Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 199 records · Page 11Linked to original sources

PubMed1997

A comparison of dialysers with low-flux membranes: significant differences in spite of many similarities.

The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan, cellulose acetate, polymethylmethacrylate (PMMA), and polycarbonate-polyether (Gambrane) membranes were compared in a multicentre cross-over clinical trial. While all four dialysers provided comparable removal of urea and creatinine, the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane. Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane, whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations. The ability to activate complement, measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex, and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three. The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation. Neutrophil degranulation, as indicated by the release of elastase-alpha 1-proteinase inhibitor, occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes. None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex. Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes, there are also significant differences. These differences may enable improvements in therapy, while allowing continued use of low-flux dialysers.

Adult↗

PubMed1997

The severity of clinical symptoms in ragweed-allergic patients is related to the extent of ragweed-induced complement activation in their sera.

We have previously reported a correlation between the extent of ragweed allergen (RWA)-induced in vitro serum complement activation and the symptom scores registered daily during the ragweed (RW)-blooming season in RW-allergic patients. The present study was performed in 22 15-17-year-old RW-allergic adolescents. Serum samples were incubated with 100 micrograms/ml RWA, and the generation of different complement activation products was measured by ELISA or RIA. Symptom scores were registered for 4 weeks during the RW-blooming season. The patients were divided according to the extent (low or high) of the generation of complement activation products, and symptom scores registered in the two groups were compared by two-way ANOVA. Significantly higher symptom scores were obtained in the high than in the low complement activation group (P values: 0.049 for C1rC1sC1inh, 0.022 for C3bBbP, 0.015 for C5b-9, 0.0001 for C3a, and 0.0008 for C5a). Similar results were obtained at the measurement performed in the sera obtained from the same patients half a year before the season (P values: 0.022 for C3bBbP, and 0.005 for C5b-9). These findings indicate that complement activation induced by the allergen may enhance the clinical symptoms of RW allergy.

Adolescent↗

PubMed1997

PrP and beta-amyloid fragments activate different neurotoxic mechanisms in cultured mouse cells.

Alzheimer's disease and prion diseases such as Creutzfeldt-Jakob disease are caused by as yet undefined metabolic disturbances of normal cellular proteins, the amyloid precursor protein and the prion protein (PrP). Synthetic fragments of both proteins, beta-amyloid 25-35 (betaA25-35) and PrP106-126, have been shown to be toxic to neurons in culture. Cell death in both cases occurs by apoptosis. Here we show that there are considerable differences in the mechanisms involved. Thus, PrP106-126 is not toxic to cortical cell cultures of PrP knockout mouse neurons whereas betaA25-35 is. The toxicity of both peptides involves Ca2+ uptake through voltage-sensitive Ca2+ channels but only PrP106-126 toxicity involves the activity of NMDA receptors. The toxicity of betaA25-35, but not PrP106-126, is attenuated by the action of forskolin. These results indicate that PrP106-126 and PA25-35 induce neuronal apoptosis through different mechanisms.

Amino Acid Sequence↗

PubMed1997

LDL hemoperfusion--a new procedure for LDL apheresis: biocompatibility results from a first pilot study in hypercholesterolemic atherosclerosis patients.

Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. In a 2 center phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically uneventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4-6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (beta-thromboglobulin [beta-TG] extrusion), and monocytes (interleukin (IL)-1beta and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study, this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.

Acrylic Resins↗

PubMed1997

LDL hemoperfusion--a new procedure for LDL apheresis: first clinical application of an LDL adsorber compatible with human whole blood.

To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 +/- 8% and triglycerides by 23 +/- 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 +/- 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.

Acrylic Resins↗

PubMed1997

Introducing high school students to neurophysiology.

University-based scientists are increasingly meeting the challenge to communicate with the public to improve general science literacy, explain their research to a lay audience, and recruit science students. At the University of Western Ontario, graduate student volunteers of Let's Talk Science have launched a project that introduces senior high school students to research presentations given by undergraduate physiology students. The project has given the undergraduate students an opportunity to present their work to an interested audience other than their peers or faculty, while it provides the high school students with positive role models and a greater awareness of postsecondary science. This project was judged a success by all participants, because many of the high school students became interested in physiology and claimed to be more confident in their ability to participate in science, and it also appeared to improve the presentation and communication skills of the undergraduates. This innovative and cost-efficient project is an effective way to demonstrate the excitement of physiology to potential future scientists while showing undergraduate students that public communication of science is not only important but can also be fun.

Adolescent↗

PubMed1997

Noninvasive prediction of intracranial pressure curves using transcranial Doppler ultrasonography and blood pressure curves.

BACKGROUND AND PURPOSE: Until now the assessment of intracranial pressure (ICP) required invasive methods. The objective of this study was to introduce an approach to a noninvasive assessment of continuous ICP curves. METHODS: The intracranial compartment was considered a "black box" system with an input signal, the arterial blood pressure (ABP), and an output signal, the ICP. A so-called weight function described the relationship between ABP and ICP curves. Certain parameters, called transcranial Doppler (TCD) characteristics, were calculated from the cerebral blood flow velocity (FV) and the ABP curves and were used to estimate this weight function. From simultaneously sampled FV, ABP, and (invasively measured) ICP curves of a defined group of patients with severe head injuries, the TCD characteristics and the weight function were computed. Multiple regression analysis revealed a mathematical formula for calculating the weight function from TCD characteristics. This formula was used to generate the ICP simulation. FV, ABP, and ICP recordings from 11 patients (mean age, 46 +/- 14 years) with severe head injury were studied. In each patient, ICP was computed by a simulation procedure, generated from the data of the remaining 10 patients. The simulation period was 100 seconds. RESULTS: Corresponding pressure trends with a mean absolute difference of 4.0 +/- 1.8 mm Hg between computed and measured ICP were observed. Shapes of pulse and respiratory ICP modulations were clearly predicted. CONCLUSIONS: These results demonstrate that this method constitutes a promising step toward a noninvasive ICP prediction that may be clinically applicable under well-defined conditions.

Adult↗

PubMed1997

[18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron emission tomography.

The objective of this study was to evaluate positron emission tomography (PET) of [18F]fluorodexoyglucose (18FDG) uptake as a measure of neonatal acute lung injury. Inasmuch as intrapulmonary sequestration of neutrophils is a hallmark of acute lung injury, quantification of neutrophil activity using 18FDG may offer a novel, in vivo technique to examine the progression and resolution of this disease. Ten newborn piglets were studied: six received bronchoalveolar lavage followed by 4 h of high pressure ventilation of create acute lung injury. Four healthy piglets served as controls. 18FDG (0.8 mCi/kg; 29.6 MBq) was given i.v. and PET (ECAT 953/31, Siemens) was performed for 90 min. During PET, all animals were sedated, paralyzed, and ventilated to maintain normal blood gases. The time course of radioactivity in lung regions and in plasma was used to calculate the rate constant for the metabolic trapping of 18FDG in tissue according to the method of C. S. Patlak. Median 18FDG influx constants were significantly higher in injured piglets (0.0187 min-1) than in control piglets (0.0052 min-1) (p < 0.01). Moreover, consistent with the 18FDG uptake data, injured piglets had moderate to severe injury on lung histology whereas control piglets had only slight and focal histologic changes. We conclude that PET of 18FDG uptake is an accurate, readily repeatable in vivo measure of neonatal acute lung injury.

Animals↗

PubMed1997

Proteolysis of insulin-like growth factors (IGF) and IGF binding proteins by cathepsin D.

Various proteinases have been postulated to function in limited proteolysis of insulin-like growth factor binding proteins (IGFBPs) contributing to the regulation of IGF bioavailability. In this study, we report on the in vitro degradation of IGFs and IGFBPs by the purified acidic aspartylprotease cathepsin D that has been shown to proteolyze IGFBP-3. Recombinant human [125I] IGFBP-1 to -5 were processed by cathepsin D to fragments of defined sizes in a concentration dependent manner, whereas IGFBP-6 was not degraded. Ligand blotting revealed that none of the IGFBP-1 or -3 fragments formed by cathepsin D retain their ability to bind IGF. By N-terminal sequence analysis of nonglycosylated IGFBP-3 fragments produced by cathepsin D, at least four different cleavage sites were identified. Some of these cleavage sites were identical or differed by one amino acid from sites used by other IGFBP proteases described. The IGFBP-3 and -4 cleavage sites produced by cathepsin D are located in the nonconserved central region. IGF-I and -II, but not the unrelated platelet-derived growth factor BB, were degraded by cathepsin D in a time and concentration-dependent manner. We speculate that the major functional site of cathepsin D is intracellular and may be involved 1) in the selected clearance either of IGFBP or IGFs via different endocytic pathways or 2) in the general lysosomal inactivation of the IGF system.

Amino Acid Sequence↗

PubMed1997

Determinants of parental authorization for involvement of newborn infants in clinical trials.

OBJECTIVE: Parents have the right to decide on behalf of their infants whether to enroll them in controlled clinical trials. We determined the degree to which such parental decisions are influenced by risk and benefit considerations compared with other factors. DESIGN: Cross-sectional survey. PARTICIPANTS: Parents who had recently given or declined consent to one of three controlled trials in the neonatal intensive care unit. INTERVENTION: Parents were asked to complete a questionnaire that consisted of 15 sociodemographic items and 13 scaled responses to statements assessing the probability and magnitude of risk and benefit as well as perceived illness severity, attitudes toward research, and the consent process. ANALYSIS: Responses were subjected to factor analysis to identify underlying constructs. The sample was then randomly split, and multiple regression was performed on each half. RESULTS: The response rate was 83% (103 of 124) for those who had consented and 86% (37 of 43) for those who had declined. Factor analysis yielded three factors: (1) illness severity, (2) perceptions of risk or benefit and attitudes to research, and (3) sociodemographic characteristics. Multiple linear regression showed a significant multiple correlation of consent decision (r = .502), but only the second factor contributed. The analyses on split halves of the sample were comparable. Thirty-two percent of all parents agreed with the statement, "I would prefer to have the doctors advise me whether my baby should be in the study, rather than asking me to decide." CONCLUSIONS: In making consent decisions on behalf of their newborn infants, parents are influenced by risk and benefit assessments, attitudes toward research, and the integrity of the consent process. Illness severity or sociodemographic characteristics do not seem to be of similar importance. Rather than making the decision alone, a significant minority of parents would prefer to have the physicians advise them whether to volunteer their infants for a clinical trial.

Attitude to Health↗

PubMed1997

Analysis of the DCC tumor suppressor gene in testicular germ cell tumors: mutations and loss of expression.

Inactivation of the DCC (Deleted in Colon Carcinoma) tumor suppressor gene by allelic loss and/or reduced expression is associated with the development of colon cancer, gliomas, gastric and prostatic malignancies. In a total cohort of 51 testicular germ cell tumors (GCT) of different histologies we analyzed restriction fragment length polymorphism (RFLP) for DCC at two specific DNA sites in 37 GCT and DCC mRNA expression compared to that of the adjacent normal testicular tissue in 41 GCT, one Leydig cell tumor and one testicular metastasis of a non-small cell lung cancer (NSCLC). Two of 17 tumors (11.7%) informative for the Msp I polymorphic site of the DCC gene and 6/25 tumors (24.0%) informative for variable number of tandem repeat (VNTR) showed loss of heterozygosity (LOH). DCC expression was analyzed by semi-quantitative polymerase chain reaction after initial reverse transcription (RT-PCR). Thirty of 41 GCT (73.1%) and both, the Leydig cell tumor and the testicular metastasis of NSCLC, had a nearly complete or total loss of DCC mRNA expression. Six of 11 (54.5%) seminomas and 24/30 (80.0%) nonseminomas had this loss of expression. Twelve of 17 (70.5%) localized tumors, 9/13 (69.2%) tumors with lymph node involvement and 9/11 (82.2%) tumors with distant metastases showed decreased or absent DCC expression. This data suggests that inactivation of the DCC gene, especially the loss of DCC expression, is associated with the development and progression of human GCT.

Gene Expression Regulation, Neoplastic↗

PubMed1997

Hypospadias repair using a modification of Beck's operation: followup.

PURPOSE: We reviewed the results of 64 cases of hypospadias repair using a modified Beck's operation with mobilization of the anterior urethra. MATERIALS AND METHODS: Patient age at correction ranged from 10 months to 12 years (mean 3.83 years). Six patients had undergone previous surgical treatments. Uroflowmetry and evaluation of the urinary stream, meatus, glans, shaft and scar formations were used as objective criteria, and grading of management and results by parents was considered subjective criteria. RESULTS: An average of 2.1 years postoperatively 59 patients were available for this followup study. The urethral meatus was positioned satisfactorily onto the distal glans in all cases and no urethrocutaneous fistulas developed. Meatal stenosis requiring meatal dilation occurred in 2 boys. In 2 cases a curved glans, and curved penis and glans, respectively, were caused by cicatricial tissue, necessitating surgical correction. Uroflowmetry was possible in 46 cases (78%). One patient with meatal stenosis had pathological flow values. All other flow rates were within the normal range. In the second case of meatal stenosis objective evaluation was impossible. In 55 cases (93%) parents judged management and results as optimal. CONCLUSIONS: Mobilization of the anterior urethra for correction of distal hypospadias with or without chordee is highly successful, less extensive, and provides an excellent cosmetic and functional result with a minimal risk of complication. Uroflowmetry is a noninvasive, objective diagnostic tool for evaluating the functional results of hypospadias repair.

Child↗

PubMed1997

[Reproductive toxicological fundamental investigations on adult male rats of the WIST/Lppt stock on the determination of swelling after administration of cadmium chloride].

The reproductive-toxic effects after an oral administration of Cadmium as Cadmium chloride on testes and epididymidis of mature Wistar rats were investigated. After daily dosages of 0.3, 0.6, 1.0 oder 2.0 mg CdCl2/kg b.w. over one or two weeks no changes of testes and epididymidis were detected in comparison with control animals by histological observations. By means of morphometrical methods significant changes of the testes from a dosage of 1.0 mg/kg b.w. and changes of the epididymidis previously a dosage of 0.3 mg/kg b.w. have been demonstrated. That means the effect level of Cadmium is higher by consideration of testes than of epididymidis. Consequently, during investigations of reproductive toxicity one hand to test both organs.

Animals↗

PubMed1997

Hepatitis G virus (HGV)--association with graft failure after hematopoietic stem cell transplantation?

A group of 28 children was investigated after hematopoietic stem cell transplantation for evidence of hepatitis G virus (HGV) infection. HGV RNA was detected in 14 of the 28 patients (50%) and persisted in 9 of 11 patients with follow-up samples for up to 32 months. Whereas thrombopoiesis was delayed in 2 of the 14 HGV-RNA-negative patients (14.3%), 6 out of 14 (42.9%) patients in the HGV-RNA-positive group had a delayed thrombopoiesis and 2 of the latter group had to be retransplanted because of complete graft failure. These were the only cases with hepatitis C virus (HCV) coinfection. Significant liver diseases were also found only in these 2 patients with HGV and HCV coinfection. These results suggest that HGV infection may significantly influence the engraftment in patients after hematopoietic stem cell transplantation, particularly if coinfection with HCV occurs.

Adolescent↗

PubMed1997

[Deficits in the support for adolescents at risk for drug addiction-- results of questioning of experts, users and adolescents].

Consumption of alcohol and illegal drugs is a widespread phenomenon in Germany. The first contact with drugs usually takes place during adolescence. Experimental use of drugs is an integral part of personal development during adolescence. The aim of this paper is to analyse the supporting infrastucture available to adolescents who are at risk of substance abuse, with special focus on its structural deficits. In addition to epidemiological data for alcohol and illegal drugs, the professional support system is described. The support system for adolescents who have already begun with experimental usage with drugs is analysed on the basis of three interview studies: 1) professionals from support and care institutions, 2) adolescents with health hazardous drug consumption patterns, and 3) those who seek the services of health care institutions. The results show that the existing treatment does not meet the needs and demands of adolescents in most cases, because the professional support institutions cannot cope with the real context of adolescent drug abuse. Recommendations for improvements of the support institutions are finally discussed.

Adolescent↗

PubMed1996

Effects of combined nimodipine and metrifonate on rat cognition and cortical EEG.

The present study investigated if short-term treatment with an L-type Ca2+-channel inhibitor, nimodipine, can stimulate cognitive functioning and cortical electroencephalograph (EEG) arousal, and potentiate the effect of a cholinesterase inhibitor, metrifonate. Pretraining administration of nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on water maze and passive avoidance behavior of young neurologically intact controls, or water maze and passive avoidance performance failure induced by scopolamine pretreatment (i.p.; 0.4 mg/kg during the water maze and 2.0 mg/kg during the passive avoidance study), medial septal lesioning, or aging. Furthermore, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on the improvement by metrifonate (10 mg/kg, p.o.) of the water maze and passive avoidance failure induced by scopolamine pretreatment or medial septal lesioning, nor did it affect the potential of metrifonate (30 mg/kg. p.o.) to improve the water maze or passive avoidance behavior of aged rats. Finally, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on spontaneously occurring thalamically generated neocortical high-voltage spindles or spectral EEG activity of young controls, nor did it alleviate the spectral EEG abnormality induced by scopolamine (0.2 mg/kg, i.p.) administration. Also, the combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10 mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced spectral EEG activity abnormalities. According to the present results, short-term treatment with nimodipine does not stimulate cognitive functions or increase cortical EEG arousal, and does not block or potentiate the propensity of metrifonate to improve cognitive performance of rats.

Animals↗

PubMed1996

Vitamin D3 reduces the apoptotic effect of IFN-gamma but does not facilitate HLA class II inducibility in RB-defective cells.

The retinoblastoma protein (RB) regulates the cell cycle by binding and inactivating the E2F transcription factors, which prevents transcription of genes required for DNA synthesis. RB has been shown to inhibit IFN-gamma-mediated apoptosis, possibly by regulating premature entry into S phase. RB is also required for high level IFN-gamma induction of HLA class II genes, which encode antigen presenting molecules, but not for other IFN-gamma inducible genes as demonstrated in previous reports describing the analysis of RB-transformants of the RB-defective cell lines, MDA-468-S4 (S4) and H2009. The IFN-gamma response of the HLA class II genes takes much longer than does the response of the other IFN-gamma inducible genes, raising the question of whether RB facilitates HLA class II inducibility by maintaining cell viability over the long time course required for HLA class II induction. Thus, we sought to learn whether IFN-gamma induced apoptosis in an RB-defective cell line could be prevented independently of RB and whether doing so would facilitate HLA class II inducibility in the RB-defective line. Our results indicated that cotreating the RB-defective S4 cells with IFN-gamma and Vitamin D3 decreased the number of cells containing subdiploid DNA compared to cells treated with IFN-gamma alone, suggesting that Vitamin D3 reduced IFN-gamma-mediated apoptosis. S4 cells cotreated with Vitamin D3 and IFN-gamma also had decreased cell detachment, further indicating that Vitamin D3 decreased IFN-gamma induced apoptosis. However, Vitamin D3 cotreatment resulted in no detectable increase in HLA-DR, the most prominent HLA class II molecule, indicating that the effect of RB on HLA class II induction is not exclusively due to its ability to inhibit IFN-gamma induced apoptosis.

Apoptosis↗

PubMed1996

A microsomal ATP-binding protein involved in efficient protein transport into the mammalian endoplasmic reticulum.

Protein transport into the mammalian endoplasmic reticulum depends on nucleoside triphosphates. Photoaffinity labelling of microsomes with azido-ATP prevents protein transport at the level of association of precursor proteins with the components of the transport machinery, Sec61alpha and TRAM proteins. The same phenotype of inactivation was observed after depleting a microsomal detergent extract of ATP-binding proteins by passage through ATP-agarose and subsequent reconstitution of the pass-through into proteoliposomes. Transport was restored by co-reconstitution of the ATP eluate. This eluate showed eight distinct bands in SDS gels. We identified five lumenal proteins (Grp170, Grp94, BiP/Grp78, calreticulin and protein disulfide isomerase), one membrane protein (ribophorin I) and two ribosomal proteins (L4 and L5). In addition to BiP (Grp78), Grp170 was most efficiently retained on ATP-agarose. Purified BiP did not stimulate transport activity. Sequence analysis revealed a striking similarity of Grp170 and the yeast microsomal protein Lhs1p which was recently shown to be involved in protein transport into yeast microsomes. We suggest that Grp170 mediates efficient insertion of polypeptides into the microsomal membrane at the expense of nucleoside triphosphates.

Adenosine Triphosphate↗