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Biomedical subjects

G Hahn

Publications and source records attributed to G Hahn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants.

We have recently introduced a novel procedure for the construction of herpesvirus mutants that is based on the cloning and mutagenesis of herpesvirus genomes as infectious bacterial artificial chromosomes (BACs) in Escherichia coli (M. Messerle, I. Crnkovic, W. Hammerschmidt, H. Ziegler, and U. H. Koszinowski, Proc. Natl. Acad. Sci. USA 94:14759-14763, 1997). Here we describe the application of this technique to the human cytomegalovirus (HCMV) strain AD169. Since it was not clear whether the terminal and internal repeat sequences of the HCMV genome would give rise to recombination, the stability of the cloned HCMV genome was examined during propagation in E. coli, during mutagenesis, and after transfection in permissive fibroblasts. Interestingly, the HCMV BACs were frozen in defined conformations in E. coli. The transfection of the HCMV BACs into human fibroblasts resulted in the reconstitution of infectious virus and isomerization of the reconstituted genomes. The power of the BAC mutagenesis procedure was exemplarily demonstrated by the disruption of the gpUL37 open reading frame. The transfection of the mutated BAC led to plaque formation, indicating that the gpUL37 gene product is dispensable for growth of HCMV in fibroblasts. The new procedure will considerably speed up the construction of HCMV mutants and facilitate genetic analysis of HCMV functions.

Chromosomes, Bacterial↗
PubMed1999

Optimizing deconvolution techniques by the application of the Münchhausen meta algorithm.

A deconvolution applied to disturbed data often gives poor results, due to fundamental difficulties associated with ill-posed problems. Many numerical and theoretical methods have been invented to circumvent this phenomenon. Their performance varies, depending on the given problem and data. The main aim of this paper is to provide a decision rule for choosing a method for deconvolution and application of this method to the same data. We have called this meta-algorithm Münchhausen. In this paper we introduce and describe for the first time the basic principle of artificial disturbance of the data in the set-up of deconvolution. We demonstrate some interesting features of the random procedure Münchhausen, such as the non parametric set-up, robustness to disturbance of the data and last but not least good performance.

Algorithms↗
PubMed1999

[Motor evoked potentials during embolization of arteriovenous malformations for the detection of ischemic complications].

Motor evoked potentials (MEP) recorded from the distal extremity muscles in response to transcranial magnetoelectrical stimulation were analyzed in a total of 10 patients during embolization of arteriovenous malformations (AVM) localized in frontal and parietal lobe (N = 5), in the temporal lobe (N = 2), in the the brain stem (N = 1), in the medulla oblongata (N = 1), and in the cerebellum (N = 1). The objective of this study was to clarify whether MEP allow reliable detection of ischemic complications during these procedures. Stable potentials as observed in 8 of 10 patients coincided in every case with an uneventful neurological outcome. Temporary significant prolongation of the central motor conduction time (CMCT) was observed in 2 patients. Both patients demonstrated a transient hemiparesis after the procedure, probably caused by ischemia. Our results clearly indicate that MEP are able to detect ischemic events during embolization of AVMs. Therefore, the use of MEP as a monitor of pyramidal function during endovascular therapeutic procedures seems to be promising.

Adolescent↗
PubMed1998

Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells.

Hematopoietic cells and their progenitors play important roles in human cytomegalovirus latency and reactivation. Latent infection has been evaluated in defined populations of myeloid-lineage-committed progenitor cells coexpressing CD33 and CD15 or CD33 and CD14 along with the dendritic cell markers CD1a and CD10. These CD33+ cell populations were found to support latency and expression of viral latency-associated transcripts and to undergo reactivation of productive viral replication when differentiated in the presence of human fibroblasts. Reactivation was also observed when myeloid cells were carried in the presence of fibroblast-conditioned medium or medium supplemented with certain cytokines (interferon gamma, tumor necrosis factor alpha, interleukin 4, or granulocyte-macrophage colony-simulating factor), suggesting that cell differentiation pathways act as determinants of reactivation. More primitive CD34+ hematopoietic cells were also found to be susceptible to viral infection and latency was maintained as these cells differentiated into CD33+-lineage-committed populations. Between 0.01% and 0.001% of CD33+ CD14+ or CD33+ CD15+ bone marrow mononuclear cells isolated from naturally infected individuals were found to express latent transcripts. Thus, cytomegalovirus is carried within a small percentage of myeloid and dendritic cell progenitors in the healthy seropositive host. Virus reactivation may be triggered by factors associated with the inflammatory response.

Antigens, CD↗
PubMed1998

Electrical impedance tomography in monitoring experimental lung injury.

OBJECTIVE: To apply electrical impedance tomography (EIT) and the new evaluation approach (the functional EIT) in monitoring the development of artificial lung injury. DESIGN: Acute experimental trial. SETTING: Operating room for animal experimental studies at a university hospital. SUBJECTS: Five pigs (41.3 +/- 4.1 kg, mean body weight +/- SD). INTERVENTIONS: The animals were anaesthetised and mechanically ventilated. Sixteen electrodes were attached on the thoracic circumference and used for electrical current injection and surface voltage measurement. Oleic acid was applied sequentially (total dose 0.05 ml/kg body weight) into the left pulmonary artery to produce selective unilateral lung injury. MEASUREMENTS AND RESULTS: The presence of lung injury was documented by significant changes of PaCO2 (40.1 mmHg vs control 37.1 mmHg), PaO2 (112.3 mmHg vs 187.5 mmHg), pH (7.35 vs 7.42), mean pulmonary arterial pressure (29.2 mmHg vs 20.8 mmHg) and chest radiography. EIT detected 1) a regional decrease in mean impedance variation over the affected left lung (-41.4% vs control) and an increase over the intact right lung (+ 20.4% vs control) indicating reduced ventilation of the affected, and a compensatory augmented ventilation of the unaffected lung and 2) a pronounced fall in local baseline electrical impedance over the injured lung (-20.6% vs control) with a moderate fall over the intact lung (-10.0% vs control) indicating the development of lung oedema in the injured lung with a probable atelectasis formation in the contralateral one. CONCLUSION: The development of the local impairment of pulmonary ventilation and the formation of lung oedema could be followed by EIT in an experimental model of lung injury. This technique may become a useful tool for monitoring local pulmonary ventilation in intensive care patients suffering from pulmonary disorders associated with regionally reduced ventilation, fluid accumulation and/or cell membrane changes.

Acute Disease↗
PubMed1998

In situ study on the pathogenesis and immune reaction of equine herpesvirus type 1 (EHV-1) infections in mice.

The mouse model was used to study the pathogenesis of equine herpesvirus type 1 (EHV-1) after primary and secondary intranasal infections. Within a few hours after infection, EHV-1 was found in nasal and olfactorial epithelium and sub-epithelial cells of the respiratory mucosa, but antigen-specific immune cells were never detected. Next to the lung, EHV-1 was transmitted early and directly to the brain, both via the olfactory route and the trigeminal nerve, but traces of degenerative or inflammatory processes were not detected there. In the lung, the immune cells residing or invading the parenchyma did not contain viral DNA or proteins. The primary immune response in the lungs was an alveolar and interstitial inflammation, dominated by the sequential appearance of neutrophils and macrophages, while the number of T and B lymphocytes remained unaltered. Within 24 hr after re-infection, lymphocytes accumulated around the blood vessels, outnumbering monocytes more than twofold, without neutrophils appearing. The lymphocytes comprised of little more B than T cells and the T cells were predominantly CD8+ cells. Those and B cells infiltrated the parenchyma. These results show the route of virus distribution and demonstrate the lack of antigen-specific immune cells in the lungs of mice after primary intranasal infection with EHV-1.

Animals↗
PubMed1998

Monitoring perioperative changes in distribution of pulmonary ventilation by functional electrical impedance tomography.

BACKGROUND: Electrical impedance tomography (EIT) is a noninvasive technique providing cross-sectional images of the thorax. We have tested an extended evaluation procedure, the functional EIT (f-EIT), to identify the local shifts of ventilation known to occur during the transition between spontaneous, controlled and assisted ventilation modes. METHODS: Ten patients scheduled for elective laparotomy were studied in the surgical ward, operating theatre and ICU during spontaneous and different modes of mechanical ventilation. Sixteen ECG electrodes were placed on the circumference of the thorax and connected with an EIT device (APT System Mark I, IBEES, Sheffield, UK). Measurements lasting 180 s were performed and f-EIT images of regional ventilation computed. The geometrical centre of ventilation was determined to quantify the regional distribution of lung ventilation during individual modes of ventilation. RESULTS: F-EIT confirmed the differences in the distribution of ventilation associated with various modes of artificial ventilation. Accentuated ventilation of the dependent lung regions was observed during spontaneous breathing, whereas a shift of the centre of ventilation to the nondependent regions was found during controlled ventilation. In the course of assisted ventilation a continuous displacement of the centre of ventilation back towards the dependent lung regions, consistent with an increased proportion of spontaneous breathing, was detected. Unassisted spontaneous breathing after weaning from mechanical ventilation resulted in a similar ventilation distribution as during tidal breathing prior to surgery. CONCLUSION: F-EIT determined the redistribution of lung ventilation during different modes of mechanical ventilation. We expect that f-EIT will become a useful noninvasive bedside monitoring technique for imaging regional ventilation in pulmonary diseased patients during mechanical ventilation.

Abdomen↗
PubMed1998

Simulation of the initial concentration-time course after intravenous application of the drug.

In this paper we present a widely applicable computational method for the description of the initial concentration-time-course after intravenous injection of a substance. The intravascular concentration-time course, r, is described as r = c0 + g x r, where the asterisk denotes the convolution operation, c0 is the concentration-time course during the first passage of the substance and g is the transport function of the body. If the body transport function is known, then the concentration-time course of a substance can be predicted. The site of interest can be chosen arbitrarily, i.e. the concentration-time course in the arterial circulation supplying any organ can be described. This might be of special interest for the optimal design of intravenous injections of contrast media, where initial concentrations at the region of interest determine the success of the diagnostic procedure.

Animals↗
PubMed1997

[LOGNORMAL-NLSQ-technique. Evaluation of a new mathematical method for determining blood volume].

This paper describes the investigation of a new mathematical method of calculating blood volume. The new method determines the blood volume by calculating the product of the mean circulation transit time. The mean transit time is calculated from the body transport function. To examine the accuracy of the LOGNORMAL-NLSQ technique, 45 concentration time curves were measured in an in vitro recirculation model with variable clearance. The calculated volume was 4% smaller than the actual volume. This may be attributed to the functional dead space within the model, and is tolerable for clinical situations. The LOGNORMAL-NLSQ technique might acquire considerable importance in future, especially since it provides accurate results very quickly.

Blood Flow Velocity↗
PubMed1997

Autoantibodies against the protease inhibitor calpastatin: a new risk factor for venous thrombosis?

Autoantibodies reactive against human calpastatin were detected by screening a cDNA expression library with the serum of a 53 year old white female patient with a history of venous thrombosis and suspected antiphospholipid syndrome. When further sera were analyzed it could be shown that > 90% of calpastatin autoantibodies, detected by Western blotting against the partial calpastatin clone, react with the C-terminal amino acids of the protein. Therefore, an ELISA based on a synthetic peptide containing the C-terminal 27 amino acids of calpastatin was developed and 205 healthy blood donors and 138 random sera from hospital patients were analyzed. A total of 11 sera (3.2%) were positive with no significant difference between the two groups (7/205 and 4/138). In 80 consecutive patients with a history of venous thrombosis 9 positive sera (11.3%; p < 0.01 vs. blood donors, p < 0.02 vs. hospital patients) were detected. Our results indicate that autoantibodies against calpastatin may constitute a so far unknown risk factor for venous thrombosis.

Adolescent↗
PubMed1997

Effect of respiration and posture on heart rate variability.

The physiological control system of the heart produces a highly complex pattern of cardiac rhythmicity which is reflected in the variability of heart rate. The aim of this study was to analyse the effects of posture and breathing frequency on the cardiac control system by various noninvasive techniques. Seven healthy subjects (24+/-5 years, mean age+/-S.D.) were studied in the supine and sitting positions while breathing spontaneously or at a fixed rate (3, 6, 12, 24, 48, 60 breaths.min(-1)). Time series of instantaneous beat-to-beat heart rates were evaluated by spectral analysis and by the dimensionless approximate entropy parameter. The total spectral power as well as the low (<0.05 Hz) and mid frequency (0.05-0.12 Hz) spectral components were higher in the sitting position. Mean approximate entropy (+/-S.D.) (0.85+/-0.15 in sitting and 0.87+/-0.16 in lying subjects) was unaffected by postural changes or breathing frequencies higher than 6 breaths x min(-1). Analysis in the frequency domain revealed that the activity of the autonomic components controlling heart rate was modified by ventilation and postural changes, whereas approximate entropy, a unique measure of the complexity and integrity of the cardiac control system, was almost unaffected by respiration and posture.

Adult↗
PubMed1996

Gravity-dependent phenomena in lung ventilation determined by functional EIT.

Gravity exerts an effect on the distribution of intrapulmonary ventilation. A study on the detection of gravity-dependent inhomogeneity of ventilation by a functional EIT technique is presented. The study was performed on five human subjects, whose ventilation distribution was modified by changes in body position. The subjects were studied during spontaneous tidal breathing. The qualitative and quantitative analysis of the functional EIT images revealed that the ventilation is higher in the dependent lung regions when compared with the non-dependent ones. These EIT findings correspond to current knowledge of the physiological behaviour of the lungs as derived from the radioactive-gas methods and raise the possibility of applying the less complicated functional EIT in future studies on ventilation distribution in the lungs. This may be of major interest in the monitoring of intensive care patients with severe pulmonary disorders.

Adult↗
PubMed1996

Local mechanics of the lung tissue determined by functional EIT.

A new functional EIT (f-EIT) evaluation technique providing information on the local dynamic behaviour of the lung is presented. Out of a series of single EIT thoracic images local time courses of the impedance change are extracted. To detect regional differences in the dynamic behaviour of the lung tissue the local time courses at different locations are related to the average time course of the impedance change over the whole thoracic cross section. The time shifts between this reference signal and the signals from separate positions are calculated from the phase information of the complex cross spectra and evaluated in terms of the local phase angle. The computed phaseshifts are imaged over the cross section creating an 'f-EIT phase image' characterizing the local dynamic properties. To relate the observed differences to the proper lung location the resulting images are presented as a combination of the f-EIT ventilation images, which represent the local amplitude of ventilation and the f-EIT phase images. The new imaging technique was tested in spontaneously breathing humans. Alterations to pulmonary dynamics were induced by changing the body posture of the subjects. The f-EIT phase imaging procedure was shown to identify lung regions with different dynamics and it is expected that this technique will also distinguish pathologically determined alterations.

Biomechanical Phenomena↗
PubMed1996

Follow-up after therapy for prostate cancer. Treating the problems and caring for the man.

With prostate cancer being diagnosed and treated in more than 300,000 men each year, the pool of long-term survivors is dramatically increasing. Because these patients are usually elderly, they are often receiving follow-up care for unrelated problems in a primary care setting. This offers the physician an excellent opportunity to assist in management of any long-term complications of therapy and in monitoring for cancer recurrence. In addition to performing follow-up evaluations, the physician can provide counseling about a number of testing and treatment issues, including the variability of prostate-specific antigen levels, the appropriateness of a watchful waiting approach to some cancers, and the management of treatment-induced incontinence and impotence, which often have a deleterious effect on quality of life but may be amenable to therapy and psychosocial support.

Aftercare↗
PubMed1995

Changes in the thoracic impedance distribution under different ventilatory conditions.

The present study was performed with the aim of checking the suitability of EIT in imaging regional thoracic impedance variations during lung ventilation under predefined conditions and to compare EIT with established reference techniques. A new technique of functional EIT imaging designed to visualize physiologically relevant information from the sequentially registered series of thoracic distributions was introduced. Experiments were performed on five spontaneously breathing healthy subjects and on 12 anaesthetized supine pigs. 16 electrodes were placed around the thorax and consecutive transthoracic impedance distributions were measured at a rate of 1 Hz (Sheffield APT system mark I, IBEES, Sheffield, UK). Several voluntary breathing manoeuvres were performed in human subjects and the tracings of local impedance were compared with standard spirometry. In animal experiments EIT was applied during artificial ventilation at different ventilation rates and during stepwise passive emptying and filling of either one or both lungs while the respiratory muscles were relaxes. Further, selective blockade of lung regions resulting in regionally reduced ventilation was performed and the capability of EIT to follow and differentiate local ventilatory disturbances was checked by reference techniques (x-ray and staining methods). The experiments revealed an overall agreement between the spirometric and impedance data in all breathing patterns performed. A linear relationship between changes of the air content of the lungs and the regional thoracic impedance was shown (intraindividual correlation coefficient range, 0.986-0.999; n = 12 animals). The functional images of the impedance distribution across the thorax reproduced adequately the typical anatomical characteristics of the pig and the human thorax. The spatial resolution of EIT functional images was sufficient to differentiate lung areas corresponding to approximately 20 ml tissue volume. EIT with the additional evaluation procedure of functional imaging was shown to be a suitable and reliable method of imaging different ventilatory conditions with the potential to become a useful tool for monitoring respiratory function.

Adult↗
PubMed1995

Using quality for daily work in ambulatory care settings.

How do we improve the delivery of quality health care? How do we continue to motivate and recognize employees who see layoffs, downsizing, reengineering, and cutbacks? Do we continue to work with obsolete systems in the same top-down management staffs used for the last 100 years? The answer is no. The answer is total quality management, continuous quality improvement, and process improvement, but with a new twist--activity-based resourcing.

Ambulatory Care Facilities↗