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Biomedical subjects

R Schosser

Publications and source records attributed to R Schosser.

At least 19 recordsLinked to original sources

Causality assessment of suspected virus transmission by human plasma products.

BACKGROUND: Causality assessment of reports on suspected virus transmission is crucial for early detection of infectious plasma products. Commonly used algorithms, such as the WHO criteria, do not meet the specific requirements for causality assessment of suspected virus transmission. STUDY DESIGN AND METHODS: A special algorithm, based on nucleic acid amplification and gene sequencing technology, effectiveness of validated virus-inactivation methods, empirical data concerning the safety record of the product, and information on batch-related infection clusters, was developed. The algorithm is focused on laboratory test results or otherwise standardized data, with few clinical data being required. To facilitate practical application, the algorithm has been converted into a graphical decision tree. RESULTS: The feasibility of the algorithm is shown by causality assessment of sample cases. Three cases are presented with the details of each case used in the 12-question checklist. The answers provided by the checklist led to the causality classification. CONCLUSION: The algorithm is a tool for evaluating reports of suspected virus transmission in a standardized manner. It thus has the potential to improve early signal detection in pharmacovigilance of plasma products by confirmation or exclusion of suspected infectivity in most cases.

Adult↗

Quantification of [(18)F]FDG uptake in the normal liver using dynamic PET: impact and modeling of the dual hepatic blood supply.

UNLABELLED: For quantification of hepatic [(18)F]FDG uptake, the dual blood supply to the liver must be considered. In contrast to the arterial input, however, the portal venous blood supply to the liver cannot be monitored directly by PET because of the inaccessibility of the portal vein on PET scans. In this study, we investigated whether the dual hepatic input can be predicted from the measurable arterial input. Moreover, we assessed the effect of different input models on the rate constants of the standard 3-compartment model describing regional uptake of FDG. METHODS: Dynamic FDG PET scanning was performed on 5 foxhounds. Activity concentrations in blood from the aorta and the portal vein were measured simultaneously using external circuits. After image reconstruction, time--activity courses were determined from the aorta and the liver. The venous input was approximated by convolving the arterial input with a notional system function describing the dispersion of the arterial input on its way through the gastrointestinal tract. On the basis of these data, 5 different hepatic input models, which pertain to a single-input as well as a dual-input scenario, were statistically compared with regard to the adequacy of the model fits to liver data and to differences in the estimated rate constants. RESULTS: Portal venous input to the liver could be approximated by convolving the arterial input function with a system function. From this function, a mean transit time of 25 s was computed for FDG to pass through the gastrointestinal tract. According to the statistical analysis, dual-input models were superior to their single-input counterparts. However, differences in the rate constants estimated for the 5 input models were in the same order as interindividual variations within the different model groups. For the dephosphorylation rate constant, a consistent value of 0.05 +/- 0.01 min(-1) was found. CONCLUSION: Dual-input models proved to be superior to single-input models with respect to the adequacy of FDG model fits to normal liver data. However, the hepatic blood supply may be approximated by the arterial input function as well, especially for the evaluation of liver lesions mainly fed by the hepatic artery.

Algorithms↗

An immediate, allergic skin reaction to aprotinin after reexposure to fibrin sealant.

BACKGROUND: The safety of fibrin tissue adhesives has been a concern since they entered wide clinical application. Most commercially available kits contain the proteolytic inhibitor, aprotinin, to stabilize the fibrin clot. A bovine protein, this substance has an allergenic potency. CASE REPORT: This case report presents a patient who had a generalized allergic skin reaction, probably triggered by aprotinin upon reexposure to fibrin sealant injected subgaleally to achieve closure of a liquor fistula after neurosurgical treatment. The serologic investigation revealed aprotinin-specific IgE and IgG. From 1990 through 1998, reports of five allergic reactions following 1 million exposures to fibrin sealant were made to the manufacturer. The clinical relevance of allergic reactions to aprotinin contained in fibrin sealants and measures to avoid them are discussed. CONCLUSION: These hypersensitivity reactions are extremely rare (incidence, 0.5/100,000 for all reactions and 0.3/100,000 for serious reactions), but they must be kept in mind as possible adverse events after repeated applications of fibrin sealants within a few weeks.

Antibodies, Anti-Idiotypic↗

Estimating the prevalence of infectious agents using pooled samples: biometrical considerations.

Pooled testing of units is a common approach in the prevalence estimation of infectious agents, which leads to a reduction of total costs of diagnostic testing. We examine how the pool size affects the statistical properties of the prevalence estimator r. Exact formulae are used to determine bias and precision of r. It is shown that with moderate pool sizes the (upward) bias of r is negligible. If there is no diagnostic error, the random error of r increases slightly with higher pool sizes, whereas if sensitivity and specificity are lower than 1, pooling may markedly decrease the random error of r. Another reason why pooling may be beneficial (and even indispensable) is that it greatly reduces the huge bias that can result if the assumed values of the sensitivity and specificity of the diagnostic test are not equal to the true values. The numerical calculations show that, in case of prevalence rates of up to 5% and total sample sizes of n > or = 500, pool sizes of about 10 to 20 are generally satisfactory from a statistical view-point. The methodological advantages and disadvantages of more complicated pooling strategies involving repeated testing of units are discussed.

Biometry↗

Annual and seasonal variation of tick-borne encephalitis virus (TBEV) prevalence in ticks in selected hot spot areas in Germany using a nRT-PCR: results from 1997 and 1998.

The prevalence of tick-borne encephalitis virus (TBEV) in Ixodes ricinus tick populations in endemic areas of Germany with the highest TBE risk is unknown. Annual and seasonal differences in TBEV prevalence have also not been studied. Against this background, in May 1997 we started a systematic virus surveillance programme in ticks collected in locations known to have a high incidence of autochthonous TBE cases. These were 5 locations in Baden-Württemberg (Black Forest) and 8 locations in Bavaria (surrounding Passau). Field-collected ticks were randomly assigned to pools of 10 adults or 20 nymphs, respectively. The tick pools were tested for the presence of TBEV-RNA using a newly developed, sensitive nested reverse transcriptase polymerase chain reaction assay (nRT-PCR). The primer pairs were selected from the 5'-terminal noncoding region, a highly conserved part of the virus. The specificity was tested by computer homology searches of sequences, as well as by sequencing of the first and the second amplificates, by Southern blot hybridisation with a DIG-labelled oligonucleotide probe, and by restriction enzyme analysis. The method has proved to be very sensitive, with a detection limit of 20 fg of TBEV RNA per PCR run, or a single positive tick. Based on biostatistical considerations a sample size of at least 1000 ticks per estimation point was chosen. The estimated TBEV prevalence and confidence intervals (CI) were calculated from the nRT-PCR results of pooled samples (10 adults or 20 nymphs) using appropriate formulae for pooled testing. In order to identify the estimated TBEV prevalence as well as to assess the influence of annual and seasonal factors on TBEV prevalence, ticks were sampled twice a year (May and September) in 1997 and 1998 at exactly identical sites. These sites were selected because they were known to have had the highest incidence of autochthonous TBE cases during the previous 10 years. On sampling days, relevant local meteorological data were also noted. In total, 8500 I. ricinus ticks were investigated in this study, 4270 (3540 nymphs, 730 adults) from the Black Forest habitats, and 4230 (3680 nymphs, 550 adults) from the Bavarian locations. In the foci near Freiburg (Black Forest), the estimated virus prevalence was relatively high in the whole tick population, during 1997 with only slight seasonal differences [3.4% (confidence interval, CI, 2.3-4.8%) in May and 2.9% (CI 1.7-4.5%) in September]. In contrast, in 1998, in the same foci the estimated TBEV prevalence was considerably lower [1.1% (CI 0.5-2.0%) in May and 0.6% (CI 0.2-1.4%) in September]. Thus, while the seasonal differences again remained low, the annual variation was marked. In the Bavarian foci in 1997, the estimated virus prevalence of the whole tick population studied was lower than in the Black Forest foci and the seasonal fluctuations were low: in May 1997 0.9% (CI 0.4-1.8%) of the ticks were positive, in September 1.1% (CI 0.5-1.9%). In 1998, in May 2.0% (CI 1.1-3.3%) of the ticks were positive, and in September 1.1% (CI 0.5-2.1%). For the whole study period, every 50th to 100th I. ricinus nymph or adult in the Passau region was calculated to give a positive signal in the nRT-PCR. The TBEV prevalence data indicate that residents and visitors of areas in Germany known for high endemic activity take a significant risk of contracting TBEV infection, if bitten by ticks. In addition, the data suggest that annual fluctuations may exist in the whole tick population studied. Seasonal fluctuations of the virus prevalence in ticks were small.

Adult↗

Diagnostic accuracy in remote expert consultation using standard video-conference technology.

An international multicenter study (Germany, Sweden, and Switzerland) was performed to investigate the feasibility and diagnostic reliability of standard video-conferencing (VC) technology for remote expert consultation in radiology. Three high-spatial-resolution films (hand-bone, mammography, chest) and two low-spatial-resolution image sets (liver CT and MRI) were studied (total 446 images taken from different examinations). The images were recorded by a video camera, transmitted via public broadband networks, and displayed on a video monitor. The resolution of the recorded images varied from 2.4 lp/mm to 4.8 lp/mm at maximum zoom. After 3-4 months, the images were reexamined using conventional light-box reading. Diagnostic reliability was evaluated by receiver operating characteristics (ROC) analysis. With video conferencing, there was a noticeable loss of diagnostic accuracy for the high-spatial-resolution films, whereas for liver CT and liver MRI images VC reading seemed to be satisfactory (average area value difference < 0.02).

Feasibility Studies↗

Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: limitations of model description.

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.

Animals↗

Determination of regional pulmonary blood flow with systemically injected nonentrapped microspheres.

Radioactive microspheres (MS) injected into the systemic circulation shunt to the venous side of the circulation and are trapped in the lung vasculature. We hypothesized that regional pulmonary perfusion could be determined by using systemically injected shunted MS. In seven anesthetized mechanically ventilated foxhounds, regional pulmonary perfusion was measured at baseline and during experimental acute respiratory distress syndrome with MS injected into both the right and left atrium (protocol 1). Methodological error of the MS technique was assessed by simultaneous injection of two different batches of MS into the right atrium (protocol 2). Measurement of perfusion during baseline and during experimental acute respiratory distress syndrome with shunted MS had a mean bias of 0.8 and 5.6% and mean precision of 19.2 and 34.7% (r = 0.94 and r = 0.95), respectively, compared with data from nonshunted MS. Simultaneous perfusion measurements displayed bias of -2.7 and 6% and precision of 8.2 and 5.3% (r = 0.98 and r = 0.99), respectively. Systemic shunt should be high for this method to prevent bronchial circulation from imposing significant error. We conclude that systemically injected MS can be used for simultaneous measurement of regional systemic and regional pulmonary perfusion, provided that MS that shunted in the first pass are measured in lung tissue.

Animals↗

Histopathology of pressure ulcers as a result of sequential computer-controlled pressure sessions in a fuzzy rat model.

This study describes the sequential histopathological changes that occur in the development of pressure ulcers experimentally induced in the fuzzy rat model. Computer-controlled pressure was applied for six hours at a maximum of five sessions, to skin over the greater trochanter of anesthetized rats. Lesions were similar, but more pronounced after the third, fourth, and fifth sessions as compared to the first or second sessions. Lesions developed first in the muscle rather than the dermis or epidermis. The lesion most often associated with pressure was necrosis of the panniculus carnosus muscle, often accompanied by damage to underlying adipose tissue. Recurrent pressure results in increasingly severe damage to the vascular system and parenchyma, consistent with an ischemia/reperfusion insult initiated through a free radical mechanism.

Animals↗

Heterogeneity of left ventricular perfusion during pulmonary edema and microembolism treated with positive end-expiratory pressure and norepinephrine.

Regional left ventricular myocardial blood flow was studied in an experimental model of pulmonary edema and microembolization (PEM) ventilated with positive end-expiratory pressure (PEEP). The analysis was based on a 3-dimensional extension of the autocorrelation function used to assess the spatial correlation (rspat) of myocardial perfusion. Experiments were performed on 8 premedicated, anesthetized and mechanically ventilated dogs. PEM was induced with oleic acid (0.01 mg/kg) and glass beads. Successive PEEP values of 10, 15 and 20 cm H2O (P20) were applied and norepinephrine (NE, 0.2-1.0 microgram min-1 kg-1) was administered after P20. Regional perfusion was measured with radioactive microspheres. The left ventricle (LV) was dissected into 256 samples. rspat was computed as the correlation of regional perfusions of samples p units apart in the apex-to-base, endo-epicardial and angular directions. Analysis was performed after anesthesia and instrumentation (control, C), P20 and NE. Control values of rspat were around 50% in the apex-to-base and angular directions and the sign was inverted in the endo-epicardial direction. A reduction of rspat to values close to zero was observed in all directions for P20 and NE. This is the typical pattern of independent distribution. Thus, the results indicate that, under the experimental conditions used, there is some degree of neighborhood dependence of regional LV myocardial blood flow. This dependence is not observed under PEM, mechanical ventilation with PEEP and NE.

Animals↗

New clinical aspects of hereditary mucoepithelial dysplasia.

Hereditary mucoepithelial dysplasia (HMD) is a multiepithelial disorder. It is transmitted as an autosomal dominant trait (McKusick: Mendelian Inheritance in Man-Catalogs of Autosomal Dominant, Autosomal Recessive, and X-Linked Phenotypes, 8th edition. Baltimore: The Johns Hopkins University Press, pp 499, 1988). HMD is characterized by variable combinations of lesions of skin, hair, orificial mucosa, gingiva, eyes, and lungs. In some previously described patients, the corneal and pulmonary lesions were progressive and led to blindness, recurrent pneumonia, and/or premature death. On light microscopy, the lesion is characterized by dyskeratosis, and, on electron microscopy, by a paucity of gap junctions and desmosomes. Here, we describe a new 5-generation kindred in which affected individuals had the same histologic characteristics but a somewhat different clinical spectrum and a more benign course. HMD should be considered in the differential diagnosis of childhood alopecia, follicular hyperkeratosis, keratoconjunctivitis, juvenile cataracts, gingival hyperemia, restrictive lung disease, and esophageal stenosis or webs.

Alopecia↗

Methodological error and spatial variability of organ blood flow measurements using radiolabeled microspheres.

The quantitative analysis of the spatial variability of organ blood flow by means of radiolabeled microspheres (MS) requires that the methodological variability ("error") of the technique (RDmeth.) is known in each individual organ. Therefore, RDmeth. was quantified (eight to nine nuclides) in 6941 tissue samples from 13 organs of three anesthetized dogs, and the relative importance of errors originating from both the stochastic nature of MS distribution (RDtheo.) and the process of quantitation of MS radioactivity (RDcounting) was assessed under varying conditions (high/low specific MS activity (SAMS); inaccurate separation of gamma spectra; large sample size). At "minimized" methodological error (experiment 2), RDmeth. of samples trapping approximately 375 MS/nuclide was 5.8% and only slightly exceeded RDtheo. (5%). RDmeth. varied in the range 2.7-7.8% in individual organs and contributed little (3.5%) to the organs' observed spatial variability of flow. In contrast, RDmeth.--due to increased RDcounting--considerably exceeded RDtheo. when SAMS was low (experiment 3), overlap of two nuclides' main photopeaks was critical (experiment 1), or counting geometry was inappropriate (pulmonary tissue samples). At the same time, the contribution of RDmeth. to spatial flow variability rose to 7.9% (experiment 3), 26.9% (experiment 1), and 15-23% (lungs). Completely artifactual measurements, as indicated by an extremely high RDmeth. of sample flow, were rarely observed (less than 0.1%). In general, our data suggest that blood flow can be measured reproducibly and with low methodological error using up to 8 nuclides, RDmeth. does not essentially contribute to the observed spatial variability of organ blood flow, and, hence, organ flow variability may be accurately quantified using the MS technique. However, if sources of error as indicated above are present, the practice of using RDtheo. as a measure of RDmeth. (thereby neglecting RDcounting) may notably underestimate true MS error and result in an overestimation of spatial heterogeneity of organ blood flow. RDmeth., therefore, should be quantified separately in each region of interest prior to the onset of a new study.

Animals↗

Perfusion of the interventricular septum during ventilation with positive end-expiratory pressure.

OBJECTIVE: To determine whether regional hypoperfusion of the interventricular septum occurs during ventilation with positive end-expiratory pressure. DESIGN: Animal study. ANIMALS: Anesthetized, closed chest dogs (n = 8). INTERVENTIONS: Induction of experimental adult respiratory distress syndrome (ARDS) and then ventilation with 10, 15, and 20 cm H2O of positive end-expiratory pressure. MEASUREMENTS AND MAIN RESULTS: Cardiac output and regional interventricular septum blood flow were assessed at control, at induction of experimental ARDS, and at each level of positive end-expiratory pressure. Ventilation with 20 cm H2O of positive end-expiratory pressure decreased cardiac output (-32% vs. control, p less than .05), and did not change absolute, but increased relative (to cardiac output) interventricular septum blood flow. During experimental ARDS and ventilation at 20 cm H2O end-expiratory pressure, there was a redistribution of flow toward the right ventricular free wall (+93%, p less than .001) and the right ventricular part of the interventricular septum (+68%, p less than .01), while flow to the left ventricular interventricular septum and to the left ventricular free wall remained unchanged. Locally hypoperfused interventricular septum areas or findings indicative of interventricular septum ischemia were not observed during positive end-expiratory pressure. CONCLUSIONS: The decrease in cardiac output during positive end-expiratory pressure is not caused by impaired interventricular septum blood supply. The preferential perfusion of the right ventricular interventricular septum indicates increased local right ventricular interventricular septum oxygen-demand and suggests that during positive end-expiratory pressure, this part of the interventricular septum functionally dissociates from the left ventricular interventricular septum and the left ventricular free wall to support the stressed right ventricle.

Animals↗

A local area network for medical research; planning, realization and experience.

This report focuses on the planning and realization of an interdisciplinary local area network (LAN) for medical research at the University of Heidelberg. After a detailed requirements analysis, several networks were evaluated by means of a test installation, and a cost-performance analysis was carried out. At present, the LAN connects 45 (IBM-compatible) PCs, several heterogeneous mainframes (IBM, DEC and Siemens) and provides access to the public X.25 network and to wide-area networks for research (EARN, BITNET). The network supports application software that is frequently needed in medical research (word processing, statistics, graphics, literature databases and services, etc.). Compliance with existing "official" (e.g., IEEE 802.3) and "de facto" standards (e.g., PostScript) was considered to be extremely important for the selection of both hardware and software. Customized programs were developed to improve access control, user interface and on-line help. Wide acceptance of the LAN was achieved through extensive education and maintenance facilities, e.g., teaching courses, customized manuals and a hotline service. Since requirements of clinical routine differ substantially from medical research needs, two separate networks (with a gateway in between) are proposed as a solution to optimally satisfy the users' demands.

Costs and Cost Analysis↗

The evaluation of radioactive microsphere data: remarks on the use of the BMDP and SAS statistical software packages.

We investigated the suitability of BMDP and SAS as an integrated tool for the evaluation of regional blood flow data obtained from the radioactive microsphere technique. Both packages were applied to a recent study on muscle blood flow with a 3-factorial design. The organization of data and files, the strategy of data reduction, and the evaluation by means of statistical and graphical techniques are shown. The method may be applied to any microsphere study design. A considerable amount of time can be saved and data integrity may be improved. The statistical quality of the results may benefit from the broad spectrum of statistical tests available.

Algorithms↗

MIC-III--an integrated software package to support experiments using the radioactive microsphere technique.

MIC-III is a versatile program system to support gamma spectrometry data management and data collection for experiments using the radioactive microsphere technique. It is mainly written in PASCAL and running on a minicomputer. Hierarchical organ dissection schemes are used for unique classification and identification of samples. For each series of experiments, up to 12 different nuclides and up to 20 different organ dissection schemes can be handled simultaneously. Sample weights are collected on-line and sample radioactivities are measured automatically by gamma spectrometry under process control. The spectra with a resolution of 1022 channels are analyzed using a modified linear regression technique and a strategy to compensate for global spectrum shifts. The spectrum deconvolution algorithm was evaluated by calculating the recovery indices for known nuclide mixtures and compared to the stripping method, matrix method and a linear regression technique using window counts. Recovery values produced by MIC-III are better balanced than those of the other methods. MIC-III showed the smallest dispersion of the recovery index and exhibited least error accumulation in case of spectrum shift. MIC-III computes regional blood flow and arterio-venous shunt, and provides interfaces to customized programs or statistical software packages for further analysis. It has successfully been employed in more than 140 experiments.

Animals↗

Right ventricular tissue PO2 in dogs. Effects of hemodilution and acute right coronary artery occlusion.

Right ventricular (RV) epicardial tissue oxygen pressure (PtO2) was measured polarographically by means of a platinum multiwire surface electrode on the in situ beating heart of ten anesthetized dogs prior to and after moderate (Hct 28%) normovolemic hemodilution (HD) with dextran 60. In five dogs the effect of acute occlusion of the right coronary artery (RCA) on PtO2 was analyzed. The PtO2 histograms at baseline revealed a bell-shaped configuration and a mean PtO2 of 46.2 +/- 7.1 mm Hg which coincides with the PtO2 on the left ventricle (LV) reported by others. After HD mean PtO2 increased to 51.4 +/- 8.5 mm Hg (P = 0.02) without alterations of the histogram's configuration. Hemodynamics and blood gas analyses were unchanged after HD. RCA ligature was followed by non-uniform changes in the PtO2 pattern. Thus, despite marked differences in external work and O2 consumption, the PtO2 in both RV and LV myocardium are similar at rest. The increase of PtO2 in the RV at reduced Hct values, which is not seen in the LV myocardium, can be related to differences in functional capillary density between both ventricles.

Animals↗