Search PubMed⌕ Search

Biomedical subjects

U Schmidt

Publications and source records attributed to U Schmidt.

At least 253 records · Page 14Linked to original sources

Na(+)-channel activators increase cardiac glycoside sensitivity in failing human myocardium.

Na(+)-channel activators increase intracellular Na+ and thereby enhance the transport rate of sarcolemmal Na+,K(+)-ATPase. We investigated the interaction of the new Na(+)-channel activator BDF 9148 (BDF) with the cardiac glycoside ouabain (OUA) in human myocardium. The influence of OUA (0.01-0.1 microM) and of OUA after prestimulation with BDF (0.1 microM, 1 microM; BDF+OUA) on isometric force of contraction (FOC, force of contraction; +T/-T, peak rate of tension increase/decay) of electrically driven (1 Hz, 37 degrees C) papillary muscle strips from terminally failing [New York Heart Association classification IV (NYHA IV) heart transplants, n = 19] human myocardium was studied. We also examined the effects of BDF and OUA on nonfailing human myocardium (brain death resulting from traumatic injury, n = 5). 0.01 microM OUA enhanced FOC only after prestimulation with BDF (NYHA IV+2.9 +/- 0.4 mN; p less than 0.01). The time until maximal (Tmax: BDF+OUA 117 min, OUA 166 min), half-maximal (T1/2max: BDF+OUA 47 min, OUA 85 min) inotropic effects and time until toxic signs (contracture, extrasystoles) occurred were significantly shorter with BDF+OUA as compared with OUA alone. BDF influenced Tmax, T1/2max, and time until toxic side effects occurred (Ttox) of the OUA-mediated inotropism in a concentration-dependent manner. Both OUA and BDF enhanced +T and -T. The effectiveness of OUA and BDF in increasing FOC was similar to that of Ca2+ (1.8-15 mM) but significantly (p less than 0.01) higher as compared with the beta-adrenoceptor-agonist isoprenaline in NYHA IV. In myocardial membranes, [3H]ouabain binding (Bmax, Kd) was not affected by BDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of the phosphodiesterase inhibitor UK 61260 on human myocardial inotropy and diastolic relaxation.

The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT, aortocoronary bypass operation, nonfailing hearts, n = 13) and in papillary muscle strips (PAP) from moderately (New York Heart Association, NYHA II-III, mitral valve replacement, n = 6) and terminally (NYHA IV, heart transplantation, n = 7) failing human hearts. For comparison, we studied the effects of UK 61260 after prestimulation with forskolin (FOR 0.03 microM) and isoprenaline (ISO 0.03 microM), as well as the effects of milrinone (MIL 1-1,000 microM), ISO (0.01-10 microM), ouabain (OUA, 0.1 microM), and Ca2+ (1.8-15 mM) in failing human myocardium alone. UK 61260 increased force of contraction (FOC), peak rate of tension increase (+T) and decay (-T) significantly (p less than 0.01) in AUT but not in PAP of NYHA II-III and NYHA IV. Only after prestimulation (FOR and ISO), was UK 61260 effective in stimulating FOC in NYHA II-III and NYHA IV. UK 61260 increased (p less than 0.01) +T and -T, resulting in a shortening of twitch time. As judged from the EC50 values, UK 61260 increased FOC more potently than MIL. The effectiveness of OUA and Ca2+ in increasing developed tension in human failing myocardium was significantly higher as compared with UK 61260. We conclude that during stimulation of the cardiac beta-adrenoceptor-adenylate-cyclase system, UK 61260 increases myocardial systolic and diastolic function in failing human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

D-dimer levels correlate with pathologic thrombosis in trauma patients.

Pathologic thrombosis, in the form of pulmonary embolism (PE) and deep venous thrombosis (DVT), causes significant morbidity and mortality in trauma patients and presents a diagnostic and therapeutic challenge because of associated conditions in these patients. This study examines the measurement of D-dimer crosslinked fibrin degradation products (D-dimer XDPs) as an indicator of hypercoagulability that places a trauma patient at risk of developing pathologic thrombosis. The time course of changes in D-dimer values after trauma normally involves an initial increase with a rapid decrease of D-dimer XDP levels to normal. Patients who then demonstrate a second rise in D-dimer values are at risk for pathologic thrombosis. Forty-one trauma patients were studied, in two groups, to evaluate the potential use of D-dimer XDP levels in evaluating the risk of pathologic thrombosis. A secondary increase in D-dimer XDP levels was found to occur in patients with PE, although sepsis and adult respiratory distress syndrome can also cause a late increase. However, D-dimer determinations appear to provide an easy, relatively inexpensive means of evaluating trauma patients for the risk of pathologic thrombosis.

Adolescent↗

On-scene helicopter transport of patients with multiple injuries--comparison of a German and an American system.

Hospital-based helicopter services from a German (GER) and an American (AMR) university-affiliated trauma center were reviewed. All patients with multiple injuries transported via helicopter from the scene to the trauma centers during a 1-year period were included. The patients were comparable regarding mechanism of injury, age, flight times, mean ISS, ISS distribution, and number of severe injuries per body region (patients with AIS score > 3 for head, thorax, and abdomen). Overall mortality was 21 of 221 (9.5%) for GER and 21 of 186 (11.3%) for AMR (NS). Survivor-based TRISS analysis yielded Z statistics of +2.459 for GER (p < 0.025) and +1.049 for AMR (NS). M statistics were 0.89 for GER, 0.874 for AMR; the W statistic +1.35 for GER. There were nine unexpected survivors (Ps < 0.50) for GER and six for AMR. There was a significantly higher (p < 0.01) number of early deaths (< 6 hours) in AMR (12; ISS = 56) than in GER (four; ISS = 64). Analysis of the prehospital data demonstrated significant differences in the mean volume of IV fluids infused: 1800 mL, GER; 825 mL, AMR (p < 0.05); rate of intubation: 82 of 221 (37.1%) GER; 24 of 186 (13.4%) AMR (p < 0.001); and thoracic decompressions: 20 of 221 (9.1%) GER; 1 of 186 (0.5%) AMR (p < 0.001). Prehospital care in the GER system is directed on scene by a trauma surgeon member of the flight crew compared with a nurse/paramedic team with remote medical control in the AMR system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Morphological and immunohistochemical findings on the frequency of intranuclear immunoglobulin inclusions (Dutcher bodies) in malignant B-cell lymphomas].

318 cases of 682 malignant B-cell lymphomas reacted positive for cIg. 66 of them showed Dutcher bodies (DB). DB were found in about 22% of plasmacytomas, 17% of immunocytomas, and in 7.5% of follicular lymphomas and polymorphic centroblastomas, respectively. Regarding only the cIg-positive cases, DB occurred in about 27% of immunocytomas, 20% of follicular lymphomas and 18% of polymorphic centroblastomas. A single case of prolymphocytic leukaemia, centrocytoma, monomorphic centroblastoma, and immunoblastoma each showed also DB. Usually, DB-positive plasmacytomas showed kappa, alpha, and J-chains. The remaining lymphomas mostly expressed kappa, my, and J-chains. In conclusion Dutcher bodies can occur with any cIg-producing B-cell lymphoma. They are not limited to immunocytomas.

Cell Nucleus↗

Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate.

The efficacy and tolerance of a garlic preparation (Sapec, Kwai) was investigated in a randomized double-blind study vs. bezafibrate. This multi-centre study was conducted in 5 general medical practices and involved 98 patients with primary hyperlipoproteinaemia. The daily doses of the active substances were 900 mg of garlic powder (standardized as to 1.3% alliin) and 600 mg of bezafibrate, respectively. The pre-phase with placebo lasted 6 weeks, the treatment period covered 12 weeks. All patients were advised to observe a low-fat "step-1 diet" for the duration of the study. The 98 case report forms allowed the statistical evaluation of total cholesterol, HDL cholesterol and triglyceride levels for 94 patients, and of LDL cholesterol values for 92 patients. In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol, in LDL cholesterol and triglycerides, and an increase in HDL cholesterol. However, there was no significant difference in the efficacies of both medication groups. Side effects were mentioned by 5 patients each in both treatment groups, none of which led to the withdrawal of the patients. Concerning the garlic preparation, there was no correlation between the perception of garlic odour and the influence on the cholesterol level.

Aged↗

[Selective occlusion of ocular neovascularization by photodynamic therapy].

Photodynamic therapy (PDT) has successfully been used to induce vascular occlusion via endothelial damage and subsequent thrombosis. To increase the selective of this method for neovascularizations, characteristics in the ultrastructure of the proliferative vessel wall allow physiological vessels to be spared and predominantly neovascularizations to be occluded: (a) Due to the disturbance of the blood-retina barrier, free dye molecules accumulate within the vascular wall. Using a dye with prolonged retention, such as phthalocyanine (CASPc), it is possible to thrombose neovascularizations 24 h post injection while leaving the physiological vasculature of the anterior segment of the rabbit eye unaffected. (b) Proliferating endothelial cells express high numbers of low-density lipoprotein (LDL) receptors. Chlorin e6 (Ce6), a potent photosensitizer, is covalently bound to LDL. Intravascularly, ce6-LDL complexes selectively label neovascular walls. Since ce6-LDL is incorporated intracellular into enzymatically active lysosomes, photothrombosis is effectively achieved at low drug and light doses in vivo. In addition, the induced damage is spatially confined to the inner vascular lining. We conclude that carrier-mediated PDT may offer a new and sensitive approach for selective treatment of intraocular neovascularizations.

Animals↗

[Hutchinson-Gilford syndrome].

A case report on a 6-year-old boy suffering from the extremely rare Hutchinson-Gilford syndrome (progeria) is presented. The results of histopathological and immunohistological examination of the scar-like skin lesions are reported. Subcutaneous amorphous nodules were eosinophilic, PAS- und elastica-negative und remained unstained with antibodies against collagen type IV, vimentin, and collagenase. The dense perivascular infiltration consisted of CD4+, CD8-, alpha-1-antichymotrypsin-, MAC 387-, and some vimentin-positive cells. Perinodular blood vessels were more abundant and had a thickened wall. Collagen bundles were swollen. The epidermis appeared atrophic with focal basal cell degeneration.

Adipose Tissue↗

Primary retroperitoneal tumors.

The pathological classification, diagnosis and therapy of primary retroperitoneal tumors are presented. Three typical cases from our clinical experience are described. Ultrasonography is the most important screening method for the early diagnosis of primary retroperitoneal tumors. Early diagnosis and total surgical excision offer the only hope for successful treatment.

Adult↗

[Idiopathic hemochromatosis: association with antigens of the HLA system].

HLA-A3 and HLA-B7 antigens were detected significantly more frequently in a group of 59 patients with idiopathic hemochromatosis than in a general population. The haplotype most commonly associated with the disease was A3B7. No differences in disease severity were to be found between homozygotic and heterozygotic carriers of this haplotype and patients with other haplotypes. An increased prevalence was also found for the HLA-A9 antigen. The haplotypes A9B7 and A9B27 were significantly more common among the patients investigated than among the general population.

Chromosome Aberrations↗

High-dose 1,2,4-triglycidylurazol given in regimens preparatory to bone marrow transplantation. A preclinical pharmacology study.

To elucidate its potential role in the framework of bone marrow transplantation, we studied the toxicologic and pharmacologic properties of high doses of the triepoxide derivate 1,2,4-triglycidylurazol (TGU) in a preclinical dog model. Dose-dependent and dose-limiting gastrointestinal toxicity occurred in a dose range between 40 and 75 mg/kg, with the lethal dose for 50% of animals (LD50) being estimated at 60 mg/kg. Severe and life-threatening hematologic toxicity developed at all dose levels examined but was generally reversible. The combination of TGU and total-body irradiation produced synergistic gastrointestinal toxicity, necessitating reductions of the TGU dose by 50% as compared with the single-agent dose. In contrast, the combination of TGU and high-dose busulfan resulted in no apparent nonhematologic synergistic toxicities. The immunosuppressive properties of TGU given in this combination enabled sustained histocompatible allogeneic marrow engraftment in three of four animals. The pharmacokinetics of TGU were not influenced by prior total-body irradiation or high-dose busulfan. We conclude that the myelotoxic, pharmacologic and immunosuppressive properties of high-dose TGU observed in this preclinical model seem to render the drug particularly suitable for use in regimens preparatory to bone marrow transplantation.

Animals↗

Lipopeptides containing 2-(palmitoylamino)-6,7-bis(palmitoyloxy) heptanoic acid: synthesis, stereospecific stimulation of B-lymphocytes and macrophages, and adjuvanticity in vivo and in vitro.

Lipopeptides, carrying the N-terminal lipoamino acid 2-(palmitoylamino)-6,7-bis(palmitoyloxy) heptanoic acid (Pam3Adh-OH, 1), were obtained by solid-phase synthesis and by synthesis in solution. 2-Amino-6,7-dihydroxyheptanoic acid (Adh) can be regarded as a methylene analogue of S-glycerylcysteine, the N-terminal amino acid of lipoprotein from the outer cell membrane of Escherichia coli (a methylene group substitutes for the sulfur atom). The lipopeptides Pam3Adh-Ser-Ser-Asn-Ala 2a-d, in which the four possible stereoisomers of Pam3Adh-OH (2S,6S)-1 (1a), (2S,6R)-1 (1b), (2R,6S)-1 (1c), and (2R,6R)-1 (1d) are linked to the naturally occurring sequence Ser-Ser-Asn-Ala of the N-terminus of lipoprotein, and also Pam3Adh-Ser-(Lys)4 [2S,6S)-3), with a peptide part rendering the molecule water soluble, were capable of stimulating murine splenocytes polyclonally in vitro, as determined in a proliferation assay and in a hemolytic plaque assay against trinitrophenylated sheep erythrocytes. The diastereomers (2S,6S)-2 and (2R,6S)-2 with S-configurated C-6 were more active than the diastereomers (2S,6R)-2 and (2R,6R)-2 with R-configurated C-6; a change of the configuration at C-2 had less effect on the stimulatory activity. (2S,6S)-2 and (2S,6S)-3 are potent immunoadjuvants. A significantly enhanced primary immune response against trinitrophenylated sheep erythrocytes was obtained in vitro at lipopeptide concentrations of about 5 micrograms/mL and an immunization dose of 10(7) sheep erythrocytes/mL. Balb/c mice, which were immunized with a mixture of ovalbumin and (2S,6S)-2 or (2S,6S)-3, respectively, had a substantially higher antiovalbumin titer 28 days after immunization than mice which had received ovalbumin, (2S,6S)-2 or (2S,6S)-3 alone. Finally, the novel lipopeptides constitute potent macrophage activators: (2S,6S)-3 was able to induce tumor cytotoxicity against the tumor cell line L929 in bone marrow derived macrophages.

Adjuvants, Immunologic↗

Piracetam in elderly motorists.

101 elderly motorists with reduced reaction capacity were examined under real traffic conditions with regard to their driving ability. They were given a daily dose of 4.8 g piracetam or placebo over a six-week period in a randomised double-blind study. The percentage of correctly solved sign-observance items, which reflects orientation and perception in real traffic conditions, increased in the placebo-treated test-group from 79.86% in the pretest to 80.07% in the retest, whereas the test subjects of the piracetam-treated group improved their performance from 77.08% to 84.16%. After being treated with piracetam for 6 weeks, the drivers showed a significantly better performance than the placebo-group. Of particular interest is the finding that the test-subjects who had scored less than 80% in the pretest improved without exception in the retest after treatment with piracetam.

Aged↗

Non-target visual event-related potentials in evaluation of children with minor head trauma.

In 50 children, 4 months to 12 years of age, with minor head trauma non-target visual event-related potentials were performed and compared to a second registration of the potentials some months later. On following-up there was a clear tendency for a relative improvement of the latencies of the endogenous potentials. In this way non-target visual event-related potentials proved to be of value in the investigation of mental impairment in early childhood.

Brain Diseases↗

Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption.

The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.

Absorption↗

Serum melatonin levels in schizophrenic and schizoaffective hospitalized patients.

Conflicting results on changes of the diurnal melatonin rhythms of patients with affective disorders have been reported in the literature. The heterogeneous data may derive from the great discrepancy in the diagnostic criteria of different authors. A study of 12 schizoaffective and chronic schizophrenic psychotic patients found a constant pattern of an obliterated nocturnal melatonin rise only in the latter group. The presence or absence of the nocturnal melatonin rise was determined in drug-free hospitalized patients and remained unchanged despite 2 months of drug treatment including large doses of neuroleptics. This finding, when confirmed in a larger number of patients, could possibly serve as a marker for the type of mental disorder, drug to be applied and response expected.

Adult↗

[Results of myocardial scintigraphy in patients with left bundle-branch block using Tl-201 and Tc-99m-MIBI].

Tl-201 myocardial scintigrams in patients with left bundle-branch block (LBBB) are frequently non-diagnostic with respect to presence or absence of coronary artery disease (CAD). The new myocardial perfusion tracer Tc-99m-MIBI requires a different protocol due to its insignificant redistribution. Therefore, scintigraphic patterns in LBBB cannot be deduced from experiences with Tl-201. In a total of 132 patients with LBBB, 81 studies were carried out with Tl-201, another 81 studies with Tc-99m-MIBI. In 30 patients both radiopharmaceuticals were employed. 72% of the Tl-201 scintigraphies in constant LBBB resulted in a reversible septal deficit and 9% in a constant septal deficit. In contrast, 70% of the Tc-99m-MIBI scintigraphies resulted in a constant septal deficit and only 19% in a reversible septal deficit. Similar "discrepancies" were found in LBBB patients in whom CAD has been angiographically excluded (N = 17). All patients, however, with LAD or RCA stenoses and constant LBBB showed reversible septal deficits with either tracer, Tl-201 (N = 12) or Tc-99m-MIBI (N = 10). It is concluded: 1) that the majority of patients with LBBB has reduced septal perfusion, 2) that this reduction is typically stress-independent in absence of CAD, and 3) that this stress-independent perfusion deficit is, in general, only differentiated from stress-induced ischemia (in case of CAD) with using the Tc-99m-MIBI protocol.

Adult↗