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Biomedical subjects

T Dengler

Publications and source records attributed to T Dengler.

At least 19 recordsLinked to original sources

[Integrated skills laboratory concept for undergraduate training in internal medicine].

BACKGROUND AND OBJECTIVE: An amendment to the German medical curriculum in April 2002 will place basic practical skills at the centre of medical training. We report here on the implementation and evaluation of an obligatory, tutor-guided, and integrated skills laboratory concept in the field of internal medicine. METHODS: To test the effectiveness of a skills laboratory training on OSCE performance a pilot study was carried out. The experimental group, of 77 students, participated in seven sessions of communication training, skills laboratory training, and bedside teaching, each lasting one and a half hours. The control group of 66 students had as many sessions but was only offered bedside-teaching. The evaluation of acceptance of skills' training as well as the related increase in individual competence is on-going (summer term 2004: n = 176 students). RESULTS: The integrated skills laboratory concept was rated at 3.5 (SD = 1.2) on a 5-point scale and was acknowledged as practice-oriented (M = 4.2; SD = 1.0) and relevant for doctors' everyday lives (M = 3.6; SD = 1.1). Increased levels of competence according to individual self-evaluations proved to be highly significant (p<.001), and results of the pilot study showed that the experimental group had a significantly better OSCE performance than the control group (p<.001). CONCLUSION: This pilot study shows that curriculum changes promoting basic clinical skills are effective and lead to an improved practical education of tomorrow's physicians. The integrated skills laboratory concept is well accepted and leads to a relevant increase in competence in the practice of internal medical. The presented skills laboratory concept in internal medicine is proving to be a viable and efficient learning tool.

Adult↗

Platelet storage solution affects on the accuracy of laboratory tests for platelet function: a multi-laboratory study.

BACKGROUND AND OBJECTIVES: Extent of shape change (ESC) and hypotonic shock response (HSR) have been widely used to characterize the in vitro function of platelets and have been shown to correlate with in vivo viability. These assays have been routinely performed using platelet-poor plasma (PPP) as the test sample diluent. Because of the increasing popularity of storing platelets in synthetic media, it is important to understand the effects of using these synthetic media as test diluents for ESC and HSR measurements. The objective of this study was to determine the effect of using platelet storage solutions vs. plasma for the in vitro testing of ESC and HSR. MATERIALS AND METHODS: Six laboratories participated in this study. Platelets were prepared by apheresis, the platelet-rich plasma (PRP) method, or derived from buffy-coats. Each platelet preparation was divided, half being stored in plasma and the other half in storage solution. ESC and HSR testing were performed in duplicate on days 1 and 5, using each of three diluents: autologous plasma; fresh-frozen plasma; or storage solution. RESULTS: For both ESC and HSR, dilutions made in each of the three diluents yielded significantly different results. Dilutions made in storage solutions were more than 30% lower for ESC and HSR than those made in autologous plasma (P < 0.0001). Dilutions made in thawed fresh-frozen plasma were more than 16% lower for ESC and HSR than those made in liquid autologous plasma (P < 0.0005). CONCLUSIONS: ESC and HSR test results are significantly affected by the test diluent. Platelets should be diluted in plasma (preferably autologous) for the in vitro testing of ESC and HSR, regardless of the media in which they are stored.

Blood Platelets↗

Clinical relevance of hepatitis G virus (HGV) infection in heart transplant patients.

To investigate whether the recently discovered hepatitis G virus (HGV) influences the clinical outcome of heart transplant recipients under immunosuppression, we determined the prevalence of HGV infections correlated with liver function and survival in 51 patients. Presence of HGV RNA and anti-E2, a marker for resolved HGV infection, were serially tested in sera from patients before and after heart transplantation (HTX) by nested RT-PCR and ELISA. Four of 51 (7.8%) patients before transplantation, and 22 of 50 patients (44%) after transplantation showed signs of persistent or resolved HGV infection. HGV infection was not associated with impairment of liver function or with patient survival. In summary, presence of HGV infection does not influence the clinical outcome in heart transplant patients.

Enzyme-Linked Immunosorbent Assay↗

Impaired ventilatory efficiency in chronic heart failure: possible role of pulmonary vasoconstriction.

BACKGROUND: Patients with chronic heart failure show impairment of ventilatory efficiency, defined as the relation between ventilation and carbon dioxide output. It is caused by ventilation of excess physiologic dead space. We hypothesized a role of active vasoconstriction in the increase of physiologic dead space, presumed to lead to alveolar hypoperfusion. METHODS AND RESULTS: In 57 patients with chronic heart failure (New York Heart Association classification II through IV, ejection fraction 25.6%+/-10.4%) and 7 control subjects, gas exchange at rest and on exercise was compared with hemodynamic measurements and, in a subgroup of 15 patients, with endothelin-1, epinephrine, and norepinephrine levels in the pulmonary and systemic circulation. Ventilatory efficiency at rest (VE/VCO2 ratio) correlated with ventilatory efficiency on exercise (VE vs VCO2 slope). Impairment of ventilatory efficiency correlated strongly negative with exercise tolerance (maximal oxygen uptake: r = -0.67) and cardiac output (r = -0.66) and positive with pulmonary hypertension (mean pulmonary artery pressure: r = 0.69, pulmonary vascular resistance: r = 0.60). None of the vasoconstrictors correlated with reduction of ventilatory efficiency in the subgroup studied. CONCLUSIONS: Impairment of ventilatory efficiency in chronic heart failure is correlated with resting pulmonary artery pressures and associated with the impairment of exercise capacity. An imbalance of pulmonary vascular tone probably leads to both pulmonary hypertension and alveolar hypoperfusion.

Adult↗

Estimated risk of transmission of hepatitis C virus by blood transfusion.

OBJECTIVE: The risk of transmitting hepatitis C (HCV) by transfusion of anti-HCV-negative screened blood was estimated for the blood donor population of Baden-Württemberg (southwestern Germany). METHODS: The data from the blood donors screened for anti-HCV and for HBsAg during 1990-1995 were analyzed. RESULTS: The prevalence of confirmed anti-HCV -positive blood donations decreased continuously during the last 5 years, reaching 121 per 100,000 blood donations. A higher anti-HCV prevalence rate was found in female than in male blood donors (p < 0.05). The estimated risk of transmitting HCV during the window period is 1:200,000 (1:97,000-1:1,400,000) for repeat donors. In 1995, the calculated risk for first-time donors was 1:20,000 (1:15,000-28,000). The incidence for HCV was 1.2 per 100,000 blood donations. CONCLUSION: The risk of transmitting hepatitis C by blood transfusion is low. Additional tests to shorten the window period to detect antibodies to HCV might increase the safety of blood transfusion.

Blood Donors↗

Anti-HCV envelope prevalence in blood donors from Baden-Württemberg.

We assess the diagnostic value of the recombinant antigens E1/E2 (heterodimer) and E2 for the screening of blood donors. For this purpose an ELISA assay was developed which used these recombinant glycoproteins as solid antigens on the microtiter plates. The anti-E1/E2 assay was able to detect 80% of the positive samples by Matrix and 87% of the PCR-positive samples. Anti-E2 was less sensitive. Fifteen percent of the indeterminate samples were anti-E1/E2 and 8% anti-E2 positive. In the case of the indeterminate samples there was no coincidence of results between these assays and the PCR. Fifty percent of seroconverters showed an anti-E1/E2-positive result with a previous indeterminate donation. We conclude that the recombinant envelope proteins, mainly anti-E1/E2, might be used in future in the diagnostics of HCV infection to increase the sensitivity of the currently used assays.

Blood Donors↗

Transferral of extrathoracic donor neoplasm by the cardiac allograft.

The transference of neoplasm from the donor to the recipient is a rare but recognized complication of organ transplantation. It has been reported after kidney transplantation from cadaver donors. We report a case in which an extrathoracic tumor was transmitted by the donor heart. The donor heart was harvested from a 46-year-old local donor and immediately transplanted to a 62-year-old female recipient. While implantation was performed, a hypernephroma was detected in the multiorgan donor. The ongoing heart transplantation could not be stopped. Four weeks after operation, the patient was discharged from the hospital. During the first year after transplantation, the clinical course was uneventful. One year after operation, the patient was admitted to the hospital with symptoms of weakness and fever. A right facial hemiparesis occurred, and a soft tumor was palpable subcutaneously in the right supraorbital region. Histologic examination revealed a malignant tumor with characteristics identical to the donor hypernephroma. In spite of chemotherapy and radiation therapy, dramatic tumor progression occurred with multiorgan metastases, which led to the death of the patient 2 months after admission.

Brain Neoplasms↗

[Perspectives of immunosuppressive therapy].

The goal of immunosuppressive therapy in organ transplantation is the achievement of transplant-specific immune tolerance. Elucidation of the molecular basis of the functions of human lymphocytes is a step towards the development of novel, more specific and less harmful measures for clinical immune intervention.

Cytokines↗

HCV transmission through blood transfusion: are HCV-RNA titer in donor serum and genotype major determinants of infection outcome?

In this paper we report the results of a retrospective investigation on anti-HCV supplemental test positive blood donors from 1993 and 1994. 22 living recipients of blood/blood components from 15 donors were localized and enrolled in the study. Serum from these individuals were tested by serological assays and RT/PCR. HCV-RNA titer was determined for all positive donors. Genotyping was performed for all HCV-RNA positive individuals (donors and recipients). We observed that less than 50% of the recipients of previous donations from those positive donors did develop serological markers of HCV infection. HCV-RNA titers in donor's serum varied from 2 x 10(3) to 5 x 10(5) copies/ml but a direct correlation between viral RNA titer and the outcome of infection could not be established. Genotype investigation revealed 100% identity of genotypes within the pairs of donors/recipients. Genotype 1 b reached a prevalence of 75% within this group.

Blood Donors↗

[Screening for increased cholesterol values in blood donors].

OBJECTIVE: In a pilot study blood donors were screened on HDL, LDL, and total cholesterol. The practicability and significance of such a screening in a blood bank should be tested. DESIGN: For this purpose, current methods to determine HDL, LDL, and total cholesterol were adapted on microtiter plates and validated. In a period of about 4 weeks all blood donors were tested for the three cholesterol parameters. SETTING: Red Cross blood bank in Baden-Baden, Germany with about 150,000 donations per year. PARTICIPANTS: The HDL, LDL, and total cholesterol results of 10,006 blood donors could be evaluated. INTERVENTIONS: None. RESULTS: The mean total cholesterol was 192 +/- 36 mg/dl, the mean HDL cholesterol 56 +/- 15 mg/dl, and a mean LDL cholesterol of 123 +/- 39 mg/dl was found. The known age-dependency of the measured cholesterol fractions could be confirmed in our blood donor population. According to the current recommendations, more than 20% of the tested blood donors need a therapy. CONCLUSIONS: The study shows that the screening of blood donors for increased total cholesterol for prevention of coronary heart disease could be done with a minimum of costs.

Adolescent↗

[HIV retrospective study of the German Red Cross blood donation service in Germany].

OBJECTIVE: It was tried to retrospectively identify HIV infections in recipients of transfusions from donors who were tested HIV positive at a subsequent donation. These lookback data were traced back to answer the following questions: 1. How many transfusion recipients were infected before the start of the routine HIV testing in 1985? 2. How great is the risk of HIV infections from infected but not yet HIV antibody-positive donors? 3. Furthermore, the transfusion of HIV-infected transfusion recipients was traced back to the involved donor to establish causality. DESIGN: Retrospective ('lookback') study. SETTING: HIV Study Group of the Red Cross Blood Banks of the Federal Republic of Germany. PARTICIPANTS: Preceding donations of HIV antibody-positive repeat donors were traced back to the transfusion recipients in order to establish their HIV antibody status. In a second lookback study, HIV-infected transfusion recipients and their corresponding donors were investigated after they had been reported to the blood bank as infected by transfusion-associated HIV. INTERVENTIONS: None. RESULTS: Recipients of 156 respectively 133 transfusions from repeat donors found to be Western blot-positive were investigated from 1985 to 1987 and from 1987 to 1992, respectively. About 50% of the recipients had died. About 40% of the recipients could not be examined, because they either were not available for testing or refused to be tested or because it was impossible to clarify the fate of the blood products. 25 HIV recipients were identified from 1981 to 1985, when routine HIV testing began. Nine transfusion-associated HIV infections were identified from 1985 to 1992. 25 million units of blood were prepared during this period. CONCLUSIONS: The risk of HIV transmission by tested transfusions is extremely rare (in the order of 1:1 million). The second lookback study suggests that in more than 50% of the blood recipients in whom HIV infection was attributed to transfusion, a causal relationship to an infected donor could not be established.

AIDS Serodiagnosis↗

[Experiences with the "verification" of anti-HCV ELISA positive blood donors].

Because there is no real conformation assay available to confirm anti-HCV ELISA reactive screening results, we have used the combination of two supplementary tests to decide which blood donors must be notified and excluded from further donations. Overall we could 'confirm' about 35% of the screening-ELISA reactive results, which means a real prevalence of 0.17% of anti-HCV in our donor population.

Blood Donors↗

Differential expression and release of LFA-3 and ICAM-1 in human melanoma cell lines.

We examined 10 different melanoma cell lines for cellular expression and release of ICAM-1 (CD54) and LFA-3 (CD58) and the influence of cytokines, including IFN alpha, IFN gamma and TNF alpha. Cellular ICAM-1 expression and density varies considerably between the melanoma cell lines. While IFN alpha has no effect on cellular ICAM-1 (cICAM-1) expression, IFN gamma and to a lesser extent TNF alpha can effectively up-regulate cICAM-1. Soluble ICAM-1 (sICAM-1) is detected in the supernatants of all lines tested, release of sICAM-1 correlates with cellular expression. LFA-3 does not much differ in its expression level on melanoma lines, and cytokines have little or no effect on its expression. Soluble LFA-3 is released by only 6 out of 10 lines. Its release can effectively be inhibited by IFN gamma in all lines and by TNF alpha in one, while IFN alpha has no effect. These data show that expression and release of LFA-3 and ICAM-1 differ between melanoma cell lines. This may be of importance for the interaction of melanoma cells with immune effector cells in vivo.

Animals↗

Core-lipid A on the K40 polysaccharide of Escherichia coli O8:K40:H9, a representative of group I capsular polysaccharides.

From the capsular K40 polysaccharide of E. coli O8:K40:H9, a fraction was obtained by gel permeation chromatography which in SDS-PAGE exhibited a ladder-like pattern characteristic of lipopolysaccharides. In Western blots, this fraction reacted with a K40-specific antiserum but not with an O8-specific antiserum. It contained, in addition to the constituents of the K40 polysaccharide (glucuronic acid, glucosamine and serine), glucose, galactose, heptose, and KDO. Mild acid hydrolysis of this fraction liberated a lipid moiety which by chemical analysis was characterized as lipid A. From these results, we conclude that the capsular polysaccharide of E. coli O8:K40:H9 is in part bound to core lipid A. The significance of this finding is discussed.

Bacterial Capsules↗

Structural studies of an emulsion-stabilizing exopolysaccharide produced by an adhesive, hydrophobic Rhodococcus strain.

The primary structure of an emulsion-stabilizing exopolysaccharide from the adhesive, hydrophobic Rhodococcus strain No. 33 was elucidated by NMR spectroscopy, methylation analyses, periodate oxidation and oligosaccharide analyses. The polysaccharide PS-33 consisted of rhamnose, galactose, glucose and glucuronic acid in molar ratios of 2:1:1:1. The main chain contained 3-substituted alpha-D-glucuronic acid linked to the 3-position at alpha-L-rhamnose, in addition to 3-substituted residues of beta-D-galactose and alpha-D-glucose. The alpha-L-rhamnose of the side chain was linked to position 4 of the galactose. In addition, the polysaccharide was O-acetylated, corresponding to one acetyl group per repeating unit. From the results two structural possibilities could be suggested. As the polysaccharide carries hydrophobic groups (methyl of rhamnose/O-acetyl), it is very likely that these are of general significance for the emulsifying activity of polysaccharides. It also seems to be possible that this polysaccharide is at least partially responsible for the hydrophobic cell surface properties of the Rhodococcus strain No. 33 and it may be involved in hydrophobic interactions when adhering to hydrophobic interfaces.

Bacterial Adhesion↗