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Biomedical subjects

G Unger

Publications and source records attributed to G Unger.

At least 19 recordsLinked to original sources

Hepatitis C virus transmission through quarantine fresh-frozen plasma.

In 1994, quarantine fresh-frozen plasma (Q-FFP) was introduced in Germany in order to reduce the risk of HIV and HCV transmission. In 1998, an acute HCV infection of a patient was reported to us. The look-back revealed that this patient had received two Q-FFP from a donor who had seroconverted for HCV in the meantime. Recipients of further plasma donations from this donor were identified. Back-up specimens of these donations were investigated in several laboratories. A total of 25 additional HCV-PCR positive plasma units had been transfused to 12 further patients. HCV infections were diagnosed in seven of these recipients, three patients had already been deceased. One of the remaining two recipients was already HCV positive prior to transfusion, in the other patient, no HCV infection was detectable. This patient had received three units of an "early" plasma donation , which was tested negative by PCR in one laboratory, but positive in the other. The subsequent, clinically infectious donation had the same discrepant PCR results. Thus, eight cases of HCV transmission were revealed and classified as "certain" with regard to causality, also due to an identical HCV genotype, i.e. 3e. Some of these infections would have been prevented by application of a different anti-HCV assay. The assay used in the respective plasmapheresis station was in-sensitive in this individual case for more than 400 days after the first PCR positive donation. This caused the release of the above mentioned infectious units. Upon re-testing the backups, three of four other anti-HCV assays revealed a positive result already 104 days after the first PCR-positive donation. The donor had increased ALAT levels (> 23 IU/L) at nine of 28 donations, two of these were higher than 2.5 times the upper normal limit, and two were higher than 68 IU/L, which is the cut-off value for male blood donors in Germany. The results of these (look-back) studies arouse several queries, i.e. differences in the diagnostic sensitivity between current anti-HCV and PCR tests, the accuracy of risk-estimates (especially when based on hemovigilance studies for Q-FFP), the value of ALAT testing, and currently practised release algorithms for Q-FFP.

Adult↗

Localization of pestiviral envelope proteins E(rns) and E2 at the cell surface and on isolated particles.

The glycoproteins E(rns) of classical swine fever virus (CSFV) and E(rns) and E2 of bovine viral diarrhoea virus (BVDV) are shown to be located at the surface of infected cells by the use of indirect immunofluorescence and by cytofluorometric analysis. The positive immunostaining of the cell surface was further analysed by immunogold electron microscopy and it could be shown that only extracellular virions were labelled. Gold granules were not seen at the cellular plasma membrane. In contrast to BVDV E2, the CSFV E2 of virions sticking to the plasma membrane was not accessible to the respective monoclonal antibodies. However, CSFV particles isolated from culture supernatant were able to bind both monoclonal anti-E(rns) and anti-E2 antibodies. For CSFV and BVDV, binding of anti-E(rns) antibodies to the virions was more pronounced than that of anti-E2. This finding was unexpected since E2 is considered to be the immunodominant glycoprotein.

Animals↗

A fully-automated environmental chamber for examination of long-term effects of intermittent hypoxia on medium-size animals.

We describe the design and construction of a fully-automated environmental chamber for the simultaneous exposure of up to four medium-size laboratory animals to long-term intermittent hypoxia. The air-sealed automated environmental chamber consists of a box equipped with a ventilation fan and three electrically-activated solenoid valves. Our system was used to expose four rabbits to 12 h of repetitive episodes of hypoxia (environmental O2 concentration 12-13%) lasting 45 min followed by breathing room air for 15 min. During environmental hypoxia, the mean arterial PaO2 and PaCO2 were 41 +/- 3.0 and 24 +/- 0.7 mmHg (mean +/- SEM), respectively. In this system, opening and closing of the solenoid valves is fully computerized to allow different settings of the duration and severity of hypoxia. The chamber is safe and fully automated and cost-effective for studying the effects of long-term intermittent hypoxemia in medium-size animals.

Animals↗

Detection of Pseudomonas aeruginosa in bronchial and tracheal aspirates by PCR by amplification of the exotoxin A gene.

For the first time, a PCR test based on the amplification of the Exotoxin A was evaluated for its ability to rapidly detect Pseudomonas aeruginosa in tracheal and bronchial aspirates from mechanically ventilated patients. The reaction is based on the amplification of a 396 bp region within the Exotoxin A gene. The results show that this PCR-method is suitable for the detection of Pseudomonas aeruginosa even in clinical samples such as aspirates. Among the 380 clinical samples tested in this way, 57 were found to be positive while only 36 were positive using routine culture. In conclusion, these results suggest that the PCR-method mentioned above can be used to provide a specific, rapid, simple, and highly sensitive detection of Pseudomonas aeruginosa in clinical samples.

ADP Ribose Transferases↗

Influence of maxillary constriction on nasal resistance and sleep apnea severity in patients with Marfan's syndrome.

BACKGROUND: Marfan's syndrome is associated with a high prevalence of obstructive sleep apnea (OSA). As this syndrome is associated with a characteristic constricted maxilla and high-arched palate, we reasoned that nasal airway constriction and resultant high nasal airway resistance (NAR) may contribute to the development of OSA. Therefore, the aim of this study was to measure NAR in patients with Marfan's syndrome. In addition, we aimed to examine the influence of maxillary morphology on both NAR and the severity of OSA. METHOD: We measured NAR in 13 consecutive patients with Marfan's syndrome and 13 control subjects. NAR was measured by posterior rhinomanometry, and expressed as the inspiratory resistance at a flow of 0.5 L/s. Dental impressions were taken to evaluate maxillary arch morphology, allowing measurement of the following distances: intercuspid (ICD), interpremolar (IPD), intermolar (IMD), and maximum hard palate height (MPH). Ten of the patients and four of the control subjects had previously undergone nocturnal polysomnography. RESULTS: Mean NAR for the Marfan group was more than twice that in the control group (7.7 +/- 1.2 vs 2.9 +/- 0.4 cm H2O/L/s; p < 0.005). The patients also had marked constriction of the maxillary arch compared with control subjects. Two of the lateral maxillary measurements were significantly inversely correlated with NAR. There were significant correlations between various maxillary arch measurements (MPH/ICD, MPH/IPD, MPH/IMD) and the apnea/hypopnea index. CONCLUSION: These data suggest that high NAR is a common feature of Marfan's syndrome. Maxillary constriction with a relatively high hard palate appears to be a major reason for the high NAR. The significant correlations between indexes of maxillary constriction and sleep apnea severity suggest that maxillary morphology may play an important role in the pathophysiology of OSA in Marfan's syndrome.

Adult↗

[A herpesvirus-caused enzootic--Pacheco's parrot disease--in a psittacine collection].

After the official confirmation of psittacosis in a collection of psittacine birds a total of 40 of them died during treatment with tetracycline. 36 of them underwent post mortem examination. From 33 birds the causative herpesvirus of Pacheco's parrot disease (PPD) was isolated and/or a non-purulent hepatitis diagnosed, the latter a characteristic for PPD. The cause of the outbreak was assumed to be a latent herpesvirus infection of individual birds which was activated by various stress factors during the psittacosis treatment. The macroscopic and histologic lesions, the results of virological investigations and the in vitro effect of acyclovir on the multiplication of the isolated herpes virus are described.

Animals↗

[Organic trace element pollution in water--a potential health risk for long-term dialysis patients].

During clinical hemodialysis patients blood is exposed in general 3 times every week to about 150 l of dialysate. The quality of the water used to prepare dialysate solution is therefore of great importance. A potential health hazard exists especially for those contaminants which are protein-bound in the blood. As a consequence, even if present in dialysate in lower concentrations than in blood that substances may still cross the dialysis membrane and accumulate in the body to toxic levels. The present paper describes the behaviour of the herbicide 2,4-dichlorophenoxyacetic acid that is known for its high plasma protein binding, during in vitro study using standard dialysis devices. The quantification of the herbicide in dialysate and plasma was performed with a radioimmunoassay.

2,4-Dichlorophenoxyacetic Acid↗

Identification of a structural glycoprotein of an RNA virus as a ribonuclease.

One of the three structural glycoproteins of classical swine fever virus (CSFV) is E0, a disulfide-bonded homodimer that induces virus-neutralizing antibodies and occurs in a virion-bound as well as a secreted form. E0 was shown to be similar to a family of fungal and plant ribonucleases. Purified E0 from CSFV-infected cells was a potent ribonuclease specific for uridine and inhibitable by zinc ions.

Amino Acid Sequence↗

Molecular characterization of positive-strand RNA viruses: pestiviruses and the porcine reproductive and respiratory syndrome virus (PRRSV).

Molecular characterization has become an important tool for the analysis of viruses including their classification. The manuscript focuses on the molecular analysis of two members of the genus pestivirus (hog cholera virus, HCV and bovine viral diarrhea virus, BVDV) and of the recently discovered porcine reproductive and respiratory syndrome virus (PRRSV). The first protein encoded within the single large pestivirus ORF is a nonstructural protein with autoproteolytic activity. The cleavage site between the protease and the capsid protein p14 has been predicted previously, but recent experimental data indicate that processing occurs at a different site. The capsid protein is followed by a putative internal signal sequence and three glycoproteins which are part of the virion envelope. According to a new proposal for the nomenclature of the structural proteins of pestiviruses they are termed C, E0, E1 and E2. The genomes of BVDV pairs isolated from animals which came down with mucosal disease were analyzed. The genomes from cytopathogenic (cp) BVD viruses may contain insertions highly homologous to cellular sequences. In addition, cp BVDV may differ from its non cytopathogenic (noncp) counterpart by mere rearrangement of viral sequences. The disease PRRS, which emerged a few years ago, is caused by a single strand RNA virus; the viral genome is of positive polarity and has a size of 15 kb. Data concerning morphology, morphogenesis and virion composition suggested already that PRRSV belongs to a group of so-called arteriviruses which comprises equine arteritis virus (EAV), lactate dehydrogenase elevating virus (LDV) and simian hemorrhagic fever virus (SHFV). This conclusion has now been confirmed by analysis of genome organization, gene expression strategy and by comparison of deduced protein sequences.

Amino Acid Sequence↗

Processing of the envelope glycoproteins of pestiviruses.

The genomic RNA of pestiviruses is translated into a large polyprotein that is cleaved into a number of proteins. The structural proteins are N terminal in this polyprotein and include three glycoproteins called E0, E1, and E2 on the basis of the order in which they appear in the polyprotein. Using pulse-chase experiments, we show that a pestiviral glycoprotein precursor, E012, is formed that is processed into E0, E1, and E2 in an ordered fashion. Processing is initiated by a nascent cleavage between the capsid and the translocated E012 followed by cleavage at the C terminus of E2. E012 is then rapidly cleaved to form E01 and E2. After E2 is released from the precursor, E01 is processed into E0 and E1. To identify the sites of cleavage, the N termini of the glycoproteins of the pestivirus classical swine fever virus (formerly termed hog cholera virus) were sequenced after expression in the vaccinia virus system. The N termini are Glu-268 for E0 (gp44/48), Leu-495 for E1 (gp33) and Arg-690 for E2 (gp55). The sequences around the cleavage sites capsid/E0 and E1/E2 conform to the rules known for cellular signal proteases, as does the sequence at the presumed C terminus of E2. The sequence upstream of the E0/E1 cleavage site also shows sequence characteristics of signalase processing sites but lacks the typical hydrophobic signal peptide; this cleavage site has characteristics in common with a site in flaviviruses that is also cleaved in a delayed fashion. The absence of any membrane-spanning region results in the shedding of E0 by infected cells, and E0 can be detected in the virus-free supernatant. Comparison of the sequences around the cleavage sites of pestiviruses suggests a general processing scheme for the structural glycoproteins. Comparison of the pesti- and flaviviral structural glycoproteins suggests analogies between E012 and prM-E.

Amino Acid Sequence↗

[Effect of molsidomine on hemodynamics in patients with dilated cardiomyopathy].

The effect of 4 mg Molsidomine iv. followed by a continuous infusion of 3 mg per hour for 3 hours on arterial blood pressure, pulmonary artery pressure, cardiac index, peripheral and pulmonary vascular resistance and heart rate was evaluated in eleven patients suffering from chronic heart failure caused by non-ischaemic dilatative cardiomyopathy (NYHA II-III). A significant decrease in systemic blood pressure, systolic and mean pulmonary artery pressure and pulmonary wedge pressure was observed and also a marked decrease in total peripheral and pulmonary vascular resistance. There was a slight, but not significant increase in cardiac index. The heart rate did not change significantly. Treatment had to be stopped in one patient because of side effects (hypotension, nausea).

Adult↗

[Angina pectoris anamnesis in patients with their first myocardial infarct].

In 650 consecutive patients with first acute myocardial infarction the time interval between the first anginal attack and the acute infarction as well as the time interval between onset of symptoms suggestive for acute myocardial infarction and hospitalization were evaluated. Our results demonstrate that in 25% of patients the history of angina was less than 24 hours, in 50% of all patients less than three days; furthermore, the time interval from onset of symptoms of acute myocardial infarction to hospitalization correlated with the history of angina; the depression of left ventricular function after myocardial infarction was independent of a previous history of angina; in patients with a very short history of angina there was a significantly higher incidence of single vessel disease. Thus, prevention of acute myocardial infarction would have been possible only in about half of the patients with impending myocardial infarction due to the short duration of preceding angina.

Adult↗

Intravenous streptokinase therapy in acute myocardial infarction: assessment of therapy effects by quantitative 201Tl myocardial imaging (including SPECT) and radionuclide ventriculography.

To evaluate a potential beneficial effect of systemic streptokinase therapy in acute myocardial infarction, 36 patients treated with streptokinase intravenously were assessed by radionuclide ventriculography and quantitative 201Tl myocardial imaging (including SPECT) in comparison with 18 conventionally treated patients. Patients after thrombolysis had significantly higher EF, PFR, and PER as well as fewer wall motion abnormalities compared with controls. These differences were also observed in the subset of patients with anterior wall infarction (AMI), but not in patients with inferior wall infarction (IMI). Quantitative 201Tl imaging demonstrated significantly smaller percent myocardial defects and fewer pathological stress segments in patients with thrombolysis compared with controls. The same differences were also found in both AMI and IMI patients. Our data suggest a favorable effect of intravenous streptokinase on recovery of left ventricular function and myocardial salvage. Radionuclide ventriculography and quantitative 201Tl myocardial imaging seem to be reliable tools for objective assessment of therapy effects.

Adult↗

Exercise test in patients over 65 years of age after the first myocardial infarction.

In 171 patients a submaximal exercise test was performed 3-6 weeks after the first acute myocardial infarction. No complications in connection with exercise test were observed. The incidence of ST/T-segment changes was significantly higher in patients over age 50. Patients over age 60 have a significantly higher incidence of PVCs as well as complex ventricular arrhythmias. In this patient group the incidence of ventricular arrhythmias was higher in patients with ST/T-segment changes during exercise. In the younger patients there was no correlation between incidence of ST/T-segment changes and arrhythmias. A high percentage of patients with no arrhythmias during exercise also had no arrhythmias during Holter. During follow up the average mortality rate was 3.6% and was not significantly different in the four age groups.

Aged↗