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Biomedical subjects

T Weber

Publications and source records attributed to T Weber.

At least 145 records · Page 8Linked to original sources
PubMed1999

Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis.

Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines. Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNFalpha by 62.5% (P< 0.0001), of IL-6 by 39% (P< 0.0001), and of IL-1beta by 40% (P= 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNFalpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-1beta and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNFalpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1999

Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity.

Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.

Adult↗
PubMed1999

Molecular cloning and expression of major structural protein VP1 of the human polyomavirus JC virus: formation of virus-like particles useful for immunological and therapeutic studies.

The major structural viral protein, VP1, of the human polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy (PML), was expressed by using recombinant baculoviruses. Recombinant VP1 formed virus-like particles (VLP) with the typical morphology of empty JCV capsids. Purified VP1 VLP bind to SVG, B, and T cells, as well as to monkey kidney cells. After binding, VP1 VLP were also internalized with high efficiency and transported to the nucleus. Immunization studies revealed these particles as highly immunogenic when administered with adjuvant, while immunization without adjuvant induced no immune response. VP1 VLP hyperimmune serum inhibits binding to SVG cells and neutralizes natural JCV. Furthermore, the potential of VP1 VLP as an efficient transporter system for gene therapy was demonstrated. Exogenous DNA could be efficiently packaged into VP1 VLP, and the packaged DNA was transferred into COS-7 cells as shown by the expression of a marker gene. Thus, VP1 VLP are useful for PML vaccine development and represent a potential new transporter system for human gene therapy.

Animals↗
PubMed1999

Long term outcome after out-of-hospital cardiac arrest with physician staffed emergency medical services: the Utstein style applied to a midsized urban/suburban area.

OBJECTIVE: To test the effect of a physician staffed advanced cardiac life support (ALS) system on patient outcome following out-of-hospital cardiac arrest. DESIGN: Observational study. SETTING: Two tier basic life support (BLS) and physician staffed ALS services in the midsized urban/suburban area of Heidelberg, Germany. PATIENTS: All patients suffering out-of-hospital cardiac arrest of cardiac aetiology between January 1992 and December 1994 and who were covered by ALS services. INTERVENTIONS: Physician staffed ALS services. MAIN OUTCOME MEASURES: Return of spontaneous circulation, hospital discharge, and one year survival, according to the Utstein style. RESULTS: Of 330 000 inhabitants, 755 suffered from cardiac arrest covered by the Heidelberg ALS services. In 512 patients, cardiopulmonary resuscitation had been initiated. Of 338 patients with cardiac aetiology, return of spontaneous circulation was achieved in 164 patients (49%), 48 (14%) were discharged alive, and 40 (12%) were alive one year later; most of these patients showed good neurological outcome. Thus, 4.85 patients with cardiac aetiology were saved by the ALS services and discharged alive per 100 000 inhabitants a year. Ventricular fibrillation or tachycardia was detected in 106 patients (31%), other cardiac rhythms in 40 (12%), and asystole in 192 (57%). Hospital discharge rates (and one year survival) in these subgroups were 34.0% (29.2%), 12.5% (7.5%), and 3.6% (3.1%), respectively. Discharge rates increased if cardiac arrest was witnessed (bystander, 20.0%; BLS/ALS personnel, 21.4%; non-witnessed arrest, 3.3%; p < 0.01), and if the time period between the alarm and the arrival of the ALS unit was four minutes or less (</= 4 minutes, 30.6%; 4-8 minutes, 10.4%; > 8 minutes, 8. 1%; p < 0.001). In 69 patients with bystander witnessed cardiac arrest with ventricular fibrillation, the discharge rate was 37.7%; 21 patients were alive after one year. CONCLUSIONS: A two tier BLS and physician staffed ALS system is associated with good long term outcome of patients suffering from out-of-hospital cardiac arrest of cardiac aetiology in a midsized urban/suburban area. Further studies, however, are required to assess whether having a physician in the ALS unit is an independent determinant for improved long term outcome.

Aged↗
PubMed1999

[Clinical presentation and coronary angiographic results in unstable angina pectoris].

The syndrome "unstable angina" (UA) covers a broad spectrum of patients. In this study we tried to determine the relationship between the severity of UA and angiographic findings. We evaluated 1000 consecutive patients undergoing coronary angiography. Those with the clinical diagnosis "UA" were included in the study. In a retrospective analysis of their records we categorized them, using the Braunwald-classification for determination of the severity of the disease. 352 patients were include, 209 men and 143 women, the mean age was 65 years. 47% met Braunwald-Class I, 26% Class II and 27% Class III. Coronary single-vessel disease was present in 29%, two-vessel disease in 20%, three-vessel disease in 25%, normal coronaries in 13% and coronary atherosclerosis without critical narrowing in 13%. Left ventricular function was preserved in 72%, mild systolic dysfunction was found in 10%, moderate in 13% and severe in 5%. There was no overall correlation between clinical presentation (Braunwald-Classes) and angiographic findings. Women showed a similar distribution of Braunwald-Classes, but significantly more coronary arteries without critical obstruction. In patients with reduced systolic function the percentage of multi-vessel disease was significantly higher, the percentage without relevant coronary artery narrowing was significantly lower. 1) The lack of overall correlation between clinical presentation and angiographic findings supports the importance of coronary angiography in the evaluation of patients with UA. 2) The assessment of women with chest pain is more difficult than of men with regard to coronary heart disease. 3) UA in patients with impaired left ventricular function is a predictor of severe coronary artery disease.

Aged↗
PubMed1999

[Therapy of heart failure with ACE inhibitors--"evidence-based medicine" and clinical reality].

Treatment of patients with chronic heart failure improves symptoms and NYHA functional class in about 50-80% of all patients treated. A 15% reduction can be observed in the need for hospitalisation and a 16-31% reduction in 1-year mortality. 37% risk reduction for progression to symptomatic heart failure can be achieved with ACE-inhibition in asymptomatic patients with systolic left ventricular dysfunction (55). Thus, ACE-inhibition should be part of standard treatment in symptomatic and asymptomatic patients with left ventricular dysfunction. In symptomatic patients with chronic heart failure, combination therapy of an ACE-inhibitor with digitalis and diuretics is state of the art and improves symptoms significantly. The addition of a vasodilatator can be considered in selected cases. Based on recently published data on beta-adrenoreceptor-blockade in the treatment of chronic heart failure, beta-blockers seem to get part of standard therapy of heart failure in the present and near future (2, 44, 50, 60). In spite of innovations of modern heart failure therapy prognosis is still bad. Survival after diagnosis of severe heart failure (functional class NYHA III and IV) is limited to a mean of 14 month.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Functional characteristics of the telemedical network for the medical service of the Bundeswehr for support of operations outside Germany and civil-military co-operation.

The maxim governing the accomplishment of medical tasks by the Medical Service of the Bundeswehr stipulates that the soldiers will, in case of illness, accident or injury, receive medical treatment to the standard they can expect in the Federal Republic of Germany. In this context the introduction of telemedical applications into the Medical Service will improve the quality of the medical care through better and faster access for the medical officer assigned to a unit or a ship for requesting support to expert knowledge from military facilities or the civilian sector. The telemedical system is based on a high-class commercial PC. This workstation can be extended as needed with medical devices (x-ray film digitizer, dermatoscope, otoscope) and allows linkage to other imaging methods (e.g., videocamera, ultrasound). Currently this system is under evaluation in a multi centre trial. The participants of this telemedical network communicate via EURO ISDN lines with sufficient bandwidth. If terrestrial lines are not available the communication will be based on satellite capacity. The application of internet-technology additionally provides access to medical data bases respectively allows civil-military co-operation and the interoperability between medical services of allied armed forces. This future-orientated telemedical approach with its modular upwards-compatibility will provide, especially in its mobile version and by using communication standards, the possibility to support necessary civil-military co-operation in the area of disaster relief and missions outside of Germany in the future.

Germany↗
PubMed1998

Impairment of peroxisomal structure and function in rat liver allograft rejection: prevention by cyclosporine.

BACKGROUND: During allograft rejection, cytokines and lipid mediators contribute to cell injury and organ failure. Peroxisomes play a crucial role in lipid metabolism, including the degradation of lipid mediators by peroxisomal beta-oxidation. Therefore, we investigated the alterations of hepatic peroxisomes after allogeneic rat liver transplantation. METHODS: MHC-incompatible Dark Agouti (RT1a) donor rats and Lewis (RT1(1)) recipient rats were used for allogeneic transplantation. For immunosuppression, a group of these animals received cyclosporine (CsA) intraperitoneally (1 mg/kg body weight per day). Lewis rats were used for isogeneic transplant combination. Ten days after transplantation, livers were investigated using morphometrical methods for determination of peroxisomal diameter and volume density. The activities of peroxisomal catalase (CAT) and acyl-coenzyme A oxidase (AOX) were determined, and the corresponding proteins were evaluated by quantitative immunocytochemistry and immunoblotting. The expressions of mRNAs encoding CAT and AOX were investigated by Northern blotting. RESULTS: The volume density and diameter of peroxisomes were significantly decreased in allogeneic transplanted livers but were unchanged in CsA-treated animals. Both the activities of CAT and AOX and their protein levels were significantly reduced in liver allografts. Moreover, the corresponding mRNA levels of CAT and AOX were decreased significantly in liver allografts, whereas CsA treatment led to an increase of those mRNAs. Isogeneic transplanted livers showed only a slight reduction of the corresponding enzyme values. CONCLUSIONS: Peroxisomes are severely affected both morphologically and functionally after allogeneic liver transplantation. These results suggest that impairment of peroxisomal lipid beta-oxidation could contribute to the pathogenesis of the rejection process by decreased catabolism of lipid mediators involved in the regulation of the inflammatory response. CsA, in addition to its immunosuppressive effects, may contribute to allograft survival by maintenance of those important peroxisomal functions.

Acyl-CoA Oxidase↗
PubMed1998

Case-control study of risk factors of Creutzfeldt-Jakob disease in Europe during 1993-95. European Union (EU) Collaborative Study Group of Creutzfeldt-Jakob disease (CJD).

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a transmissible spongiform encephalopathy. Genetic and iatrogenic forms have been recognised but most are sporadic and of unknown cause. We have studied risk factors for CJD as part of the 1993-95 European Union collaborative studies of CJD in Europe. METHODS: The 405 patients with definite or probable CJD who took part in our study had taken part in population-based studies done between 1993 and 1995 in Belgium, France, Germany, Italy, the Netherlands, and the UK. Data on putative risk factors from these patients were compared with data from 405 controls. FINDINGS: We found evidence for familial aggregation of CJD with dementia due to causes other than CJD (relative risk [RR] 2.26, 95% CI 1.31-3.90). No significant increased risk of CJD in relation to a history of surgery and blood transfusion was shown. There was no evidence for an association between the risk of CJD and the consumption of beef, veal, lamb, cheese, or milk. No association was found with occupational exposure to animals or leather. The few positive findings of the study include increased risk in relation to consumption of raw meat (RR 1.63 [95% CI 1.18-2.23]) and brain (1.68 [1.18-2.39]), frequent exposure to leather products (1.94 [1.13-3.33]), and exposure to fertiliser consisting of hoofs and horns (2.32 [1.38-2.91]). Additional analyses, for example stratification by country and of exposures pre-1985 and post-1985, suggest that these results should be interpreted with great caution. INTERPRETATION: Within the limits of the retrospective design of the study, our findings suggest that genetic factors other than the known CJD mutations may play an important part in CJD. Iatrogenic transmission of disease seems rare in this large population-based sample of patients with CJD. There is little evidence for an association between the risk of CJD and either animal exposure, or consumption of processed bovine meat or milk products for the period studied.

Adult↗
PubMed1998

SNAREpins: minimal machinery for membrane fusion.

Recombinant v- and t-SNARE proteins reconstituted into separate lipid bilayer vesicles assemble into SNAREpins-SNARE complexes linking two membranes. This leads to spontaneous fusion of the docked membranes at physiological temperature. Docked unfused intermediates can accumulate at lower temperatures and can fuse when brought to physiological temperature. A supply of unassembled v- and t-SNAREs is needed for these intermediates to form, but not for the fusion that follows. These data imply that SNAREpins are the minimal machinery for cellular membrane fusion.

Bacterial Proteins↗
PubMed1998

Diagnosis of Creutzfeldt-Jakob disease by measurement of S100 protein in serum: prospective case-control study.

OBJECTIVE: To analyse serum concentrations of brain specific S100 protein in patients with Creutzfeldt-Jakob disease and in controls. DESIGN: Prospective case-control study. SETTING: National Creutzfeldt-Jakob disease surveillance unit. SUBJECTS: 224 patients referred to the surveillance unit with suspected Creutzfeldt-Jakob disease and 35 control patients without dementia. MAIN OUTCOME MEASURE: Serum concentration of S100 protein in patients with Creutzfeldt-Jakob disease, in patients with other diseases causing dementia, and in the control group. RESULTS: Of the 224 patients with suspected Creutzfeldt-Jakob disease, 65 were classed as definitely having the disease after neuropathological verification, an additional 6 were classed as definitely having the disease as a result of a genetic mutation, 43 as probably having the disease, 36 as possibly having the disease, and 74 patients were classed as having other disease. In the 108 patients classed as definitely or probably having Creutzfeldt-Jakob disease the median serum concentration of S100 was 395 pg/ml (SD 387 pg/ml). This was significantly higher than concentrations found in the 74 patients classed as having other diseases (median 109 pg/ml; SD 177 pg/ml; P = 0.0001). At a cut off point of 213 pg/ml sensitivity for the diagnosis of the disease was 77.8% (95% confidence interval 68.8% to 85.2%) and specificity was 81.1% (70.3% to 89.3%). There was a significant difference in survival at different concentrations of S100 in Kaplan-Meier curves (P = 0.023). CONCLUSION: Measurement of serum concentrations of S100 is a valuable tool which can be used more easily than tests on cerebrospinal fluid in the differential diagnosis of Creutzfeldt-Jakob disease. More studies are needed to determine whether serial testing of serum S100 improves diagnostic accuracy.

Biomarkers↗
PubMed1998

Detection of 14-3-3 protein in the cerebrospinal fluid supports the diagnosis of Creutzfeldt-Jakob disease.

The analysis of 14-3-3 protein in cerebrospinal fluid (CSF) was shown to be highly sensitive and specific for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, the predictive value of this test in the clinical diagnosis of, and its relation to, sporadic, genetic, and iatrogenic CJD cases have yet to be established. CSF samples of suspect CJD cases seen in the prospective German surveillance study were tested for the presence of 14-3-3 protein by using a modified western blot (WB) technique. WB detected 14-3-3 protein in 95.4% of definite and 92.8% of probable cases. In two patients classified initially as not having CJD the test was positive, and both were later proved to have definite CJD. The positive predictive value is 94.7% and the negative predictive value is 92.4%. False-positive results in a single CSF analysis were seen in patients with herpes simplex encephalitis, hypoxic brain damage, atypical encephalitis, intracerebral metastases of a bronchial carcinoma, metabolic encephalopathy, and progressive dementia of unknown cause. WB analysis for 14-3-3 protein was positive in only 5 of 10 cases of familial forms of spongiform encephalopathies. CSF analysis for 14-3-3 protein should thus be performed in any case suspect for CJD.

14-3-3 Proteins↗
PubMed1998

Late results of heterotopic autotransplantation of splenic tissue into the greater omentum.

There is still controversy about the beneficial effects of splenic autotransplantation. As a result, replantation of the spleen has almost been abandoned for surgical treatment of splenic injuries. To learn more about the long-term effects we have analyzed eight patients 9.2 +/- 1.2 years after autotransplantation of the spleen into the greater omentum. Splenic replants could be detected by scintigraphy in seven patients (87.5%). Splenic size, measured by single-photon emission computed tomography, varied between 19.344 and 471.705 units of volume (Uov). Two patients with the smallest replants had pathologic changes of leukocytes and lymphocyte subsets in 12 of 16 measurements (75%). These changes closely resembled a spleenless state and were similar to those in the patient with no detectable splenic autograft. In contrast, five patients with large splenic replants (49.192-471.705 UoV) revealed pathologic findings in only 2 of 40 measurements (5%). Based on an extensive review of the literature and our own results, it can be concluded that splenic autotransplantation into the greater omentum is superior to splenectomy but undoubtedly less effective than in situ preservation of the spleen. Therefore splenic replantation should still be considered, particularly in pediatric surgery, when in situ preservation of the spleen is not possible by other techniques.

Adolescent↗
PubMed1998

Bronchiolitis obliterans organizing pneumonia and ulcerative colitis after allogeneic bone marrow transplantation.

A 37-year-old man with acute myeloblastic leukemia in first remission developed ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7 months after bone marrow transplantation (BMT) from an HLA-matched brother who suffered from severe Crohn's disease. BOOP occurred 20 days after idiopathic interstitial pneumonia, in the context of severe ulcerative colitis. Lung and colon biopsies showed no signs of CMV infection or GVHD. The patient was treated with oral methylprednisolone 1 mg/kg/day and his clinical status and chest X-ray improved slowly. Remarkably, the symptoms of colitis also resolved with prednisone therapy and he is now symptom-free. We hypothesize that ulcerative colitis may have been transmitted from donor to recipient (adoptive autoimmunity) and that it was complicated by BOOP. However, other factors such as CMV may have contributed to the occurrence of BOOP.

Adoptive Transfer↗
PubMed1998

Herpes simplex virus infections of the central nervous system in human immunodeficiency virus-infected patients: clinical management by polymerase chain reaction assay of cerebrospinal fluid.

A duplex polymerase chain reaction (PCR) assay for DNA from herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) was applied to cerebrospinal fluid (CSF) from 918 human immunodeficiency virus (HIV)-infected patients with neurological symptoms. HSV-1 or HSV-2 (HSV-1/2) DNA was found in 19 patients (2%). For the 258 patients for whom a diagnosis was confirmed at autopsy, the sensitivity and specificity of PCR analysis for the diagnosis of HSV-1/2 encephalitis were 100% and 99.6%, respectively. Three patients with CD4+ cell counts of > or = 170/microL had HSV-1 central nervous system (CNS) infections (two) or HSV-2 meningitis (one). Sixteen patients with CD4+ cell counts of < 40/microL had HSV-1 CNS infections (two) or mixed HSV-1/2 and cytomegalovirus encephalitis (14). The response to antiviral treatment, which was assessed clinically and by CSF PCR analysis, was variable in the patients with the highest CD4+ cell counts and poor in those with more severe immunosuppression. CSF PCR analysis is of value for the diagnosis and follow-up of treatment of HSV-1/2 CNS infections in HIV-infected patients.

AIDS-Related Opportunistic Infections↗