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Biomedical subjects

E Bauer

Publications and source records attributed to E Bauer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Spatial variation of au coverage as the driving force for nanoscopic pattern formation.

Au induced faceting of a 4 degrees vicinal Si(001) surface was studied with chemical resolution using soft x-ray photoemission electron microscopy. For the first time a direct and quantitative determination of the local Au coverage in situ and during deposition was possible. Au atoms, necessary for the expansion of (001) terraces, are accummulated from a lattice gas, resulting in a phase separation between Au enriched terraces and Au depleted step bunches. During a second stage Au also adsorbs on the step bunches and transforms them into (119) facets. A simple Monte Carlo simulation shows that the initial coverage difference between terraces and bunches determines the regularity of the formed mesoscopic grating.

Journal Article↗
PubMed2001

Heat-induced superaggregation of amphotericin B modifies its interaction with serum proteins and lipoproteins and stimulation of TNF-alpha.

The purpose of the present study was to examine the influence of heat-induced superaggregation of Amphotericin B (AmB) in the Fungizone (FZ) formulation on its interaction with human serum components and relate this to reduced toxicity. Whole serum distribution studies showed that a significantly lower percentage of AmB from HFZ was recovered in the high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride-rich lipoprotein (TRL) fractions and a greater percentage recovered in the lipoprotein-deficient plasma (LPDP), though the majority of both preparations were recovered in LPDP. Circular dichroism (CD) and difference absorption spectroscopy were used to determine the stability of FZ and heat-treated FZ (HFZ) in the presence of HDL, LDL, serum, and albumin. The CD studies indicate that the "core" aggregate of HFZ is more stable in the presence of HDL and LDL, whereas the FZ is less stable and more dynamic with the core aggregate dissociating to a greater extent in the presence of either purified lipoprotein. Absorption studies with whole serum and purified albumin suggest that FZ aggregates are far less stable in the presence of albumin than HFZ and that interaction with serum albumin is a dominant feature for both drug preparations. HFZ also has a different effect on the cytokine response in vitro. Studies using THP-1 human monocytes show that HFZ provokes a smaller release of tumor necrosis factor (TNF)-alpha than FZ. This cytokine may be associated with the unpleasant side effects of AmB. These findings suggest that heat-induced superaggregation of AmB alters its interaction with HDL, LDL, serum proteins, and monocytes, and these findings may be important in explaining the reduced toxicity of the superaggregated form of AmB.

Amphotericin B↗
PubMed2001

Time-dependency of sensory evoked potentials in comatose cardiac arrest survivors.

OBJECTIVE: To assess the validity of early sensory evoked potential (SEP) recording for reliable outcome prediction in comatose cardiac arrest survivors within 48 h after restoration of spontaneous circulation (ROSC). DESIGN AND SETTING: Prospective cohort study in a medical intensive care unit of a university hospital. PATIENTS: Twenty-five comatose, mechanically ventilated patients following cardiopulmonary resuscitation MEASUREMENTS AND RESULTS: Median nerve short- and long-latency SEP were recorded 4, 12, 24, and 48 h after ROSC. Cortical N20 peak latency and cervicomedullary conduction time decreased (improved) significantly between 4, 12, and 24 h after resuscitation in 22 of the enrolled patients. There was no further change in short-latency SEP at 48 h. The cortical N70 peak was initially detectable in seven patients. The number of patients with increased N70 peak increased to 11 at 12 h and 14 at 24 h; there was no further change at 48 h. Specificity of the N70 peak latency (critical cutoff 130 ms) increased from 0.43 at 4 h to 1.0 at 24 h after ROSC. Sensitivity decreased from 1.0 at 4 h to 0.83 at 24 h after ROSC. CONCLUSION: Within 24 h after ROSC there was a significant improvement in SEP. Therefore we recommend allowing a period of at least 24 h after cardiopulmonary resuscitation for obtaining a reliable prognosis based on SEP.

Adult↗
PubMed2001

He-Ne laser irradiation protects B-lymphoblasts from UVA-induced DNA damage.

The effect of He-Ne laser (632.8 nm) pre-irradiation on UVA (343 nm)-induced DNA damage in the human B-lymphoblast cell line NC37 was investigated using the comet assay. He-Ne laser pre-irradiation was observed to result in a dose-dependent decrease in UVA-induced DNA damage. This effect was also found to be dependent on the incubation period between He-Ne laser pre-irradiation and the UVA exposure. Whereas the control cells with a higher DNA damage point to an initial ability of faster repair, both the control and the He-Ne laser pre-irradiated cells subsequently show the same rate of DNA repair. The results suggest that He-Ne laser irradiation protect the cells from UVA-induced DNA damage primarily through an influence on processes that prevent an initial DNA damage.

B-Lymphocytes↗
PubMed2001

The effect of serum albumin on amphotericin B aggregate structure and activity.

PURPOSE: Mild heat treatment of Fungizone (FZ, an amphotericin B:deoxycholate preparation) leads to a new self-associated form (HFZ) that demonstrates improved therapeutic index in vivo. The origin of the improvement may lie in the differential stability in the presence of serum proteins. The purpose of this study is to assess the effect of human serum albumin (HSA) on the structure and stability and in vitro channel forming ability of these two preparations against model fungal and mammalian membrane vesicles. METHODS: Kinetic absorption and CD spectroscopy were used to assess the kinetic and equilibrium stability of the characteristic amphotericin B complexes in the presence of HSA. Kinetic fluorescence spectroscopy of pyranine entrapped in model fungal and mammalian membrane vesicles was used to measure the cation-selective channel forming ability of HZ and HFZ delivered from HSA. RESULTS: It is shown that FZ is rapidly converted from its aggregated form to a protein-bound monomer in the presence of HSA, whereas HFZ demonstrates greater stability by persisting as a stable inactive aggregate. Fluorescence measurements of ion currents show that HSA attenuates the membrane-activity of both preparations. However, the activity of both HFZ and FZ remains significant against ergosterol-containing membranes. This is the first direct measurement of the intrinsic channel forming abilities of these amphotericin B preparations in the presence of serum proteins. CONCLUSION: These data provide a mechanistic rationale for the similar efficacy and lower toxicity of HFZ.

Amphotericin B↗
PubMed2001

Monitoring gene therapy with reporter gene imaging.

Rapid advances in imaging technologies and gene transfer strategies offer a great opportunity to optimize clinical trials of human gene therapy. Reporter genes are emerging as very powerful tools to monitor the delivery, magnitude, and time variation of therapeutic gene transfer in vivo. Several reporter genes, such as the herpes simplex virus type 1 thymidine kinase, the dopamine type 2 receptor, and the somatostatin receptor type 2, are currently being successfully used with gamma camera, single photon emission computed tomography, and positron emission tomography imaging. These reporter genes can be coupled with a therapeutic gene of interest to indirectly monitor the expression of the therapeutic gene. Finally, applications of the reporter gene technology to other areas, such as cell trafficking studies and transgenic animal models, are now possible.

Animals↗
PubMed2001

8-[18F]Fluoropenciclovir: an improved reporter probe for imaging HSV1-tk reporter gene expression in vivo using PET.

UNLABELLED: We have synthesized and evaluated 8-[18F]fluoropenciclovir (FPCV) and compared it with 8-[18F]fluoroganciclovir (FGCV) for monitoring the expression of herpes simplex virus type 1 thymidine kinase (HSV1 -tk) reporter gene in cell culture and in vivo. METHODS: C6 rat glioma cells stably transfected with HSV1-tk (C6-stb-tk+) and control C6 cells were evaluated for their ability to accumulate FGCV versus FPCV. For in vivo studies, 15 mice were injected by tail vein with increasing levels of an adenoviral vector carrying HSV1-tk. Forty-eight hours later the mice were injected with FPCV and killed 3 h later. The percentage injected dose per gram (%ID/g) liver was then determined. Two additional mice were studied by microPET and autoradiography using FPCV to image adenoviral-mediated hepatic HSV1-tk reporter gene expression. A tumor-bearing mouse (C6 control and C6-stb-tk+) was imaged with FDG, FGCV, and FPCV. Two mice carrying tumors expressing two different reporter genes, HSV1-tk and dopamine type 2 receptor (D2R), were also imaged by microPET using FPCV (day 1) and 3-(2'-[18F]fluoroethyl)spiperone (FESP) (day 2). RESULTS: FPCV shows a significantly greater accumulation in C6-stb-tk+ cells than does FGCV (P < 0.05). Over identical ranges of adenoviral administration, mouse liver shows a higher %ID/g liver for FPCV (0%-9%) compared with our previously reported results with FGCV (0%-3%). In C6 control and C6-stb-tk+ tumor-bearing mice, FPCV has a greater accumulation than does FGCV for equal levels of HSV1-tk gene expression. In mice carrying tumors expressing either HSV1-tk or D2R reporter genes, there is a corresponding retention of FPCV and FESP, respectively. CONCLUSION: These results indicate that FPCV is a better reporter probe than is FGCV for imaging lower levels of HSV1 -tk gene expression in vivo. The results also reveal the ability to monitor the expression of two distinct reporter genes in the same animal using reporter probes specific for each gene.

Acyclovir↗
PubMed2001

A controlled study of sorbent suspension dialysis in chronic liver disease and hepatic encephalopathy.

To investigate the role of extracorporeal detoxification in cirrhotic patients with advanced hepatic encephalopathy not responding to medical treatment, 20 patients were randomized to receive six hours of additional sorbent dialysis or ongoing standardized medical treatment. Following treatment, the clinical stage of encephalopathy remained unchanged in both groups. Abnormal sensory evoked potentials improved following sorbent dialysis (N70 latency, 128 ms before versus 110 ms after treatment, P<0,05; cervico-cranial transmission, 7.7 ms versus 6.8 ms, P<0.01) indicating improvement in important aspects of cerebral function. In contrast, brain function remained unchanged following medical treatment (N70 latency, 114 ms versus 113 ms; cervico-cranial transmission, 7.7 ms versus 7.2 ms, P=NS, respectively). Serum benzodiazepine levels decreased significantly after sorbent dialysis but not after medical treatment. Biocompatibility of sorbent dialysis was limited and clinical complications occurred in a proportion of patients. In conclusion, a six-hour treatment with sorbent suspension dialysis did not ameliorate the clinical stage of HE but improved neurophysiologic function in cirrhotic patients who had not responded to conventional medical treatment.

Adult↗
PubMed2000

Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma.

Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified gamma delta T-cell ligands, we examined the stimulatory capacity of bisphosphonates to gamma delta T cells and determined whether gamma delta T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative response of gamma delta T cells to aminobisphosphonates was IL-2 dependent, whereas activation of gamma delta T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-gamma delta T cells was evident (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating gamma delta T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)

Alendronate↗
PubMed2000

Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium.

Experimental studies have shown that in hypertrophy and heart failure, accumulation of microtubules occurs that impedes sarcomere motion and contributes to decreased ventricular compliance. We tested the hypothesis that these changes are present in the failing human heart and that an entire complex of structural components, including cytoskeletal, linkage, and extracellular proteins, are involved in causing functional deterioration. In explanted human hearts failing because of dilated cardiomyopathy (ejection fraction </=20%), expression of alpha- and beta-tubulin, desmin, vinculin, fibronectin, and vimentin was determined by Northern and Western blot analysis and compared with normal myocardium from explants not used for transplantation. The mRNA for alpha- and beta-tubulin was increased to 2.4-fold (P<0.01) and 1.25-fold (NS), respectively; for desmin, 1.2-fold (P<0.05); for fibronectin, 5-fold (P<0.001); and for vimentin, 1.7-fold (P<0.05). Protein levels for alpha-tubulin increased 2.6-fold (P<0.02); for beta-tubulin, 1.2-fold (P<0.005); for desmin, 2.1-fold (P<0.001); for vinculin, 1.2-fold (P<0.005); for fibronectin, 2.9-fold (P<0.001); and for vimentin, 1.5-fold (P<0. 005). Confocal microscopy showed augmentation and disorganization of all proteins studied. In combination with the loss of myofilaments and sarcomeric skeleton previously reported, these changes suggest cardiomyocyte remodeling. Increased fibronectin and elevated interstitial cellularity (vimentin labeling) indicate progressive fibrosis. The present results suggest a causative role of cytoskeletal abnormalities and myofilament loss for intrinsic contractile and diastolic dysfunction in failing hearts.

Adult↗
PubMed2000

A mutant herpes simplex virus type 1 thymidine kinase reporter gene shows improved sensitivity for imaging reporter gene expression with positron emission tomography.

We are developing assays for noninvasive, quantitative imaging of reporter genes with positron emission tomography (PET), for application both in animal models and in human gene therapy. We report here a method to improve the detection of lower levels of PET reporter gene expression by utilizing a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) as a PET reporter gene. The HSV1-sr39tk mutant was identified from a library of site-directed mutants. Accumulation (net uptake) of the radioactively labeled substrates [8-(3)H]penciclovir ([8-(3)H]PCV), and 8-[(18)F]fluoropenciclovir (FPCV) in C6 rat glioma cells expressing HSV1-sr39tk is increased by a factor of approximately 2.0 when compared with C6 cells expressing wild-type HSV1-tk. The increased imaging sensitivity of HSV1-sr39tk when FPCV is used is also demonstrated in vivo both with tumor cells stably transfected with either HSV1-tk or HSV1-sr39tk, and after hepatic delivery of HSV1-tk or HSV1-sr39tk by using adenoviral vectors. The use of HSV1-sr39tk as a PET reporter gene and FPCV as a PET reporter probe results in significantly enhanced sensitivity for imaging reporter gene expression in vivo.

Acyclovir↗
PubMed2000

From majority to minority and vice versa: the asymmetrical effects of losing and gaining majority position within a group.

Two studies examined the effects of stable, partially changed, and completely changed majority and minority positions within a group on perception and evaluation of the group. It was hypothesized that loss of majority position (majority-to-minority change) would have stronger effects than gain of majority position (minority-to-majority change). The hypothesized asymmetrical effect was demonstrated in that loss of majority position decreased perception of group-self similarity, group attraction, and expectations for positive interactions with the group, whereas a corresponding gain of position did not increase them. Thus immediately following changes, the group is especially fragile because disintegrative forces created by the loss of majority position are stronger than integrative forces created by the gain of majority position.

Adult↗
PubMed2000

Risk of injury through snowboarding.

OBJECTIVE: Survey of a group of snowboarders and study of their injuries, as well as analysis of the risk of injury considering the time spent on the snowboard. MATERIALS AND METHODS: Of 7,221 students participating in winter sport programs organized by Austrian schools, 2,745 of those riding snowboards were asked to fill out questionnaires pertaining to demographics, their experience level, equipment, snowboard riding habits, and associated injuries. RESULTS: A total of 2,579 snowboarders (94%), who spent a total of 10,119 days snowboarding, filled out a questionnaire which could be evaluated. A total of 152 snowboarders had suffered a mean of 10.6 injuries per 1,000 days of snowboarding, which required medical care; 5.4/1,000 injuries were moderate or severe. The most common injuries were to the wrist (32%), the hand (20%), and the head (11%). The rate of injury was especially high during the first half-day (roughly 3 hours). Use of wrist protection devices reduced injuries to the wrist from 2 to 0.5% (p = 0.048). CONCLUSION: Risk of snowboard related injury was highest in beginners. Through the use of wrist protection devices, the incidence of the most common injuries was dramatically reduced.

Adolescent↗
PubMed2000

Lead contamination of imported candy wrappers.

Lead toxicity in a young Hispanic woman from sucking on a terra cotta candy container led to investigating lead contamination in candy packaging materials imported from Mexico. Printed cellophane candy wrappers may present a significant risk for lead exposure.

Candy↗
PubMed1999

Imaging adenoviral-directed reporter gene expression in living animals with positron emission tomography.

We are developing quantitative assays to repeatedly and noninvasively image expression of reporter genes in living animals, using positron emission tomography (PET). We synthesized positron-emitting 8-[18F]fluoroganciclovir (FGCV) and demonstrated that this compound is a substrate for the herpes simplex virus 1 thymidine kinase enzyme (HSV1-TK). Using positron-emitting FGCV as a PET reporter probe, we imaged adenovirus-directed hepatic expression of the HSV1-tk reporter gene in living mice. There is a significant positive correlation between the percent injected dose of FGCV retained per gram of liver and the levels of hepatic HSV1-tk reporter gene expression (r2 > 0.80). Over a similar range of HSV1-tk expression in vivo, the percent injected dose retained per gram of liver was 0-23% for ganciclovir and 0-3% for FGCV. Repeated, noninvasive, and quantitative imaging of PET reporter gene expression should be a valuable tool for studies of human gene therapy, of organ/cell transplantation, and of both environmental and behavioral modulation of gene expression in transgenic mice.

Animals↗
PubMed1999

[In Process Citation]

Video-assisted thoracoscopic surgery is now recommended for the treatment of primary spontaneous pneumothorax. We studied the validity of this method at our general surgical department in a prospective group with regard to effectiveness and complication rate. The combination of thoracoscopic bulla resection with tetracycline pleurodesis resulted in a 100% recurrence-free rate of 28 pneumothoraces at a median follow-up of 19 months. We observed no intraoperative complications. We conclude that video-assisted thoracoscopic surgery is an effective treatment for primary spontaneous pneumothorax and can safely be carried out even in a general surgical unit. The legal aspects are discussed in detail.

Journal Article↗