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Biomedical subjects

K Schmidt

Publications and source records attributed to K Schmidt.

At least 253 records · Page 14Linked to original sources
PubMed1996

[Status of the endoprosthesis in rheumatic metacarpophalangeal joints. Long-term results of metacarpophalangeal prostheses using Swanson's silastic spacers].

Advanced rheumatoid destruction of the metacarpophalangeal joints frequently requires implant arthroplasty. Among many different types of implants, the Swanson-Silastic-spacer is widely used. The long-term results of 102 arthroplasties of the metacarpophalangeal joint were assessed in 28 rheumatoid patients (34 hands) 10.1 years postoperatively on the average. Marked relief of pain was found in all patients. 75% of the patients reported functional improvement of the hand. Active range of motion decreased from 42 degrees preoperatively to 36 degrees postoperatively on the average. Ulnar drift was corrected from an average of 34 degrees preoperatively to 12 degrees postoperatively. The average extension deficit had improved from 33 degrees at surgery to 11 degrees at the time of follow-up. Grip strength remained unchanged. The radiographical findings showed surrounding osteolysis in 89.4% of the implants and 27.5% broken spacers. In comparison to other types of finger implants, Silastic-spacers showed similarly limited all over results, however, there seem to be less problems in salvage procedures.

Activities of Daily Living↗
PubMed1995

Bile-independent absorption of cyclosporine from a microemulsion formulation in liver transplant patients.

A microemulsion formulation of CsA, which was anticipated to be independent of bile for oral absorption, was compared with the currently marketed formulation in liver transplant patients with external biliary drainage. Eleven patients aged 47.6 +/- 13.1 years and weighing 75.8 +/- 5.7 kg received single 400-mg oral doses of each formulation in a randomized, crossover protocol on days 4 and 6 after transplant. Serial venous blood samples were collected over a 12-hr period after each administration and whole blood CsA concentrations were determined by a validated RIA specific for the parent compound. Systemic exposure to CsA was consistently higher from the microemulsion formulation in all patients, as judged by the peak concentration and the area under the curve. Specifically, the area under the concentration-time curve was 943 +/- 400 vs. 2378 +/- 911 ng.hr/ml, indicating an average 156% higher bioavailability from the microemulsion compared with the currently marketed formulation in liver transplant patients in the absence of bile.

Absorption↗
PubMed1995

Expression of interleukin-11 and its encoding mRNA by glioblastoma cells.

Interleukin-11 (IL-11) is a pleiotropic cytokine with important effects on hematopoietic and other cells. IL-11 was originally described as a product of stromal cell lines and fibroblasts. Using RT-PCR, Northern blotting, and ELISA we demonstrated that the human U373 and U87 glioblastoma cell lines expressed IL-11 and its encoding mRNA when stimulated with IL-1 beta, phorbol ester, and calcium ionophore. The neuroblastoma cell line SH-SY5Y did not express IL-11 mRNA in response to these agents. Cerebral expression of IL-11 by glial cells is important because IL-11 has been shown to have effects on neuronal electrophysiology, has overlapping functions with the neuroactive cytokine interleukin-6, and is part of the gp130-associated neuropoietic family of cytokines.

Astrocytes↗
PubMed1995

Structural analysis of porcine brain nitric oxide synthase reveals a role for tetrahydrobiopterin and L-arginine in the formation of an SDS-resistant dimer.

Nitric oxide synthases (NOSs), which catalyze the formation of the ubiquitous biological messenger molecule nitric oxide, represent unique cytochrome P-450s, containing reductase and mono-oxygenase domains within one polypeptide and requiring tetrahydrobiopterin as cofactor. To investigate whether tetrahydrobiopterin functions as an allosteric effector of NOS, we have analyzed the effect of the pteridine on the conformation of neuronal NOS purified from porcine brain by means of circular dichroism, velocity sedimentation, dynamic light scattering and SDS-polyacrylamide gel electrophoresis. We report for the first time the secondary structure of NOS, showing that the neuronal isozyme contains 30% alpha-helix, 14% antiparallel beta-sheet, 7% parallel beta-sheet, 19% turns and 31% other structures. The secondary structure of neuronal NOS was neither modulated nor stabilized by tetrahydrobiopterin, and the pteridine did not affect the quaternary structure of the protein, which appears to be an elongated homodimer with an axial ratio of approximately 20/1 under native conditions. Low temperature SDS-polyacrylamide gel electrophoresis revealed that tetrahydrobiopterin and L-arginine synergistically convert neuronal NOS into an exceptionally stable, non-covalently linked homodimer surviving in 2% SDS and 5% 2-mercaptoethanol. Ligand-induced formation of an SDS-resistant dimer is unprecedented and suggests a novel role for tetrahydrobiopterin and L-arginine in the allosteric regulation of protein subunit interactions.

Allosteric Regulation↗
PubMed1995

Peroxynitrite-induced accumulation of cyclic GMP in endothelial cells and stimulation of purified soluble guanylyl cyclase. Dependence on glutathione and possible role of S-nitrosation.

Peroxynitrite (ONOO-) is widely recognized as mediator of NO toxicity, but recent studies have indicated that this compound may also have physiological activity and induce vascular relaxation as well as inhibition of platelet aggregation. We found that ONOO- induced a pronounced increase in endothelial cyclic GMP levels, and that this effect was significantly attenuated by pretreatment of the cells with GSH-depleting agents. In the presence of 2 mM GSH, ONOO- stimulated purified soluble guanylyl cyclase with a half-maximally effective concentration of about 20 microM. In contrast to the NO donor 2,2-Diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), ONOO- was completely inactive in the absence of GSH, indicating that thiol-mediated bioactivation of ONOO- is involved in enzyme stimulation. Studies on the reaction between ONOO- and GSH revealed that about 1% of ONOO- was non-enzymatically converted to S-nitrosoglutathione. The authentic nitrosothiol was found to be stable in solution, but slowly decomposed in the presence of GSH. GSH-induced decomposition of S-nitrosoglutathione was apparently catalyzed by trace metals and was accompanied by a sustained release of NO and a 40-100-fold increase in its potency to stimulate purified soluble guanylyl cyclase. Our data suggest that the biologic activity of ONOO- involves S-nitrosation of cellular thiols resulting in NO-mediated cyclic GMP accumulation.

Animals↗
PubMed1995

Purification and characterization of a low molecular weight endogenous glutamate binding inhibitor (LGBI) in porcine brain.

One of the endogenous substances which modulate glutamate receptor binding was isolated and highly purified from porcine brain. The purification involved extraction of brain tissue with doubled distilled water, followed by gel filtration, anion exchange, cation exchange, and several steps of C18 reverse-phase high performance liquid chromatography (HPLC). A low molecular weight glutamate binding inhibitor (LGBI) was purified to apparent homogeneity as judged from the elution profile of an HPLC column, in which a symmetrical peak was obtained when the eluate was monitored at 220 nm. The LGBI appears to be a small molecule (< 2 kD) that is heat- and acid/base-stable. The highly purified LGBI has no effect on GABAA and benzodiazepine receptor binding. The LGBI is not L-glutamate, L-aspartate or other negatively charged endogenous substances, since they are clearly separated from the LGBI in anion exchange chromatography. The inhibitory effect of the LGBI on [3H]L-glutamate binding is reversible, and it only changes the Bmax while the Kd remains the same. Since the membrane preparations used for [3H]L-glutamate binding assays for the detection of LGBI activity were enriched with quisqualate (QA)-sensitive subtypes, it was suggested that the LGBI could be a modulator of the QA receptor. Some amino acids which produce significant inhibition of glutamate binding activity were also compared with the LGBI, and they all showed no resemblance to the LGBI. The chemical structure of the LGBI remains to be determined.

Amino Acids↗
PubMed1995

Kinetics and mechanism of tetrahydrobiopterin-induced oxidation of nitric oxide.

A Clark-type nitric oxide-sensitive electrode was used for electrochemical determination of NO oxidation kinetics. Reaction with molecular oxygen followed second-order rate law with respect to NO with an overall rate constant of 9.2 +/- 0.33 x 10(6) M-2 s-1. Tetrahydrobiopterin, an essential cofactor of NO synthases, was found to induce rapid oxidation of NO in a 1:1 stoichiometry. The reaction required the presence of oxygen, was zero order with respect to NO and first order with respect to tetrahydrobiopterin, completely blocked by 5,000 units/ml superoxide dismutase, and mimicked by a superoxide-generating system. Purified brain NO synthase produced no detectable NO unless high amounts of superoxide dismutase were present. NO synthase-catalyzed citrulline formation was inhibited by superoxide dismutase (5,000 units/ml) in an oxyhemoglobin-sensitive manner, indicating that NO induces feedback inhibition of NO synthase. NO-stimulated soluble guanylyl cyclase was inhibited by tetrahydrobiopterin at half-maximally active concentrations of 2 microM. The present data suggest that NO is inactivated to peroxynitrite by superoxide generated in the course of tetrahydrobiopterin autoxidation.

Amino Acid Oxidoreductases↗
PubMed1995

Apolipoprotein E genotypes in Parkinson's disease with and without dementia.

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.

Age of Onset↗
PubMed1995

Microbial production of specifically ring-13C-labelled 4-hydroxybenzoic acid.

When transformed with a recombinant vector carrying the ubiC gene (encoding chorismate pyruvate-lyase, EC 4.1.3.27) the triple mutant (Phe-, Trp-, Tyr-) Klebsiella pneumoniae 62-1 excretes 4-hydroxybenzoic acid instead of chorismic acid. The recombinant strain can be used to produce in high yield specifically ring-labelled 4-hydroxybenzoic acid from isotopically labelled glucose.

Anthranilate Synthase↗
PubMed1995

[Quality comparison of modified neurolept-, balanced and intravenous anesthesia. 1. Study design and patient analysis of the Krefelder study 1992].

The choice of appropriate anaesthesia in a more or less seriously ill patient requires detailed information on the risk and tolerance of each specific anaesthetic regimen. The objective of this prospective, randomised clinical trial was to test the hypothesis that three regimens of general anaesthesia--neurolept-(NLA), balanced (BAL), and intravenous propofol anaesthesia (IVA)--differ with regard to safety and comfort. The criteria for the intraoperative safety and postoperative comfort of the patients were the incidents, events and complications (IEC) that required medical treatment as well as the evaluation of postoperative complaints by the patients according to the IEC list and patient questionnaires of the German Society of Anaesthesia and Critical Care Medicine (DGAI). METHODS. The study duration was about 4 months, from January to April 1992. During this period the patients of all nine operative departments of the hospital received strictly randomised NLA, BAL, or IVA. Patients who had regional anaesthesia or were not capable of understanding the German language, were nonco-operative, or were seriously ill (ASA class IV to V) as well as children under 18 years of age did not participate in the study. All eligible patients provided their informed consent. ANAESTHESIA. For premedication 10 mg chlorazepate was administered the night before and on the day of surgery. Anaesthesia was conducted under normoventilation using a mixture of 70% nitrous oxide and 30% oxygen. NLA patients were induced intravenously with 0.2 mg/kg body weight etomidate and received 0.005 mg/kg fentanyl and 0.07 mg/kg droperidol before the start of surgery. The repetition dose was 0.2 mg fentanyl and 2.5 mg droperidol. In the BAL patients the dose of fentanyl and droperidol was reduced to 50% due to the addition of isoflurane up to 1 vol. %. IVA patients received 2 mg/kg propofol over 3 min followed by an infusion of 3-5 mg/kg per hour together with 0.2 mg fentanyl/h. Neuromuscular blockade was accomplished with vecuronium 0.1 mg/kg. If the blood pressure and heart rate increased by more than 20% of preoperative values, analgesia was reinforced by an additional fentanyl dose. Anaesthesia was subsequently enhanced by increasing the neurolept/propofol/isoflurane dose by up to 50%. DATA COLLECTION. The following parameters were registered: patients' personal data and physical condition according to ASA classification; the grade of risk according to the Munich risk checklist; the frequency of IEC during surgery; the patients' permanent medications; postanaesthetic vigilance and recovery; the acceptance of the assigned anaesthetic by the physician; the cost of the anaesthetic used; and pre- and post-operative complaints as well as the assessment of anaesthesia by the patient. The statistical evaluation was performed using the chi-square test. RESULTS. A total of 1,346 patients were enrolled in the study; 28 (2%) were excluded because the treatment protocol was changed by the anaesthesiologist. Seventy per cent were recruited from general, gynaecologic, or otorhinolaryngologic surgery. The three anaesthetic regimens (NLA, BAL, and IVA) were used in other departments with the same frequency with the exception of ophthalmology and urology (P > 0.1) (Fig. 1). Of the 1,318 eligible patients, 443 received NLA, 443 BAL, and 432 IVA (P = 0.8). The distribution of the various parameters was surprisingly similar among the three groups: the average age was 50 years (P = 0.91), body weight 71 kg (P = 0.33), reference or initial blood pressure 130/80 mm Hg (P = 0.36), average time of anaesthesia 103 min (P = 0.82), and all had the same risk score (P = 0.42). Sixty per cent were female. An average of 85% of the 18- to 89-year-old patients were considered to be healthy according to the ASA risk classification (P = 0.42). However, on applying the Munich risk checklist the average number of healthy individuals was 5% to 10% lower than that of the ASA risk classification.

Adolescent↗
PubMed1995

[Qualitative comparison of modified neurolept-, balanced and intravenous anesthesia. 2. Results of a clinical study, 1992].

The safety and tolerance of neuroleptanaesthesia (NLA), balanced anaesthesia (BAL), and intravenous anaesthesia with propofol (IVA) were analysed for the first time in a prospective, randomised clinical trial. METHODS. In all, 1318 surgical patients received either NLA, BAL, or IVA. Patients who had regional anaesthesia, were aged under 18 years, or were non-cooperative or vitally threatened (ASA class i.v. to V) did not participate in the study. Premedication and anaesthetic course were set up at a standard of 30% oxygen and 70% nitrous oxide. Incidents, events, and complications due to anaesthesia were obtained (IEC key of the German Society of Anaesthesia and Critical Care Medicine, DGAI). Furthermore, postanaesthetic alertness based on specific recovery tests and the quality of anaesthesia from the patient's viewpoint, rated by patient questionnaires from the DGAI were evaluated. All parameters were calculated and checked for statistical significance using the chi-square test. RESULTS AND DISCUSSION. The groups were broadly comparable with respect to age (P = 0.91), ASA class (P = 0.42), preoperative blood pressure (P = 0.36), and length of anaesthesia (P = 0.82). The anaesthesia, which averaged 103 min, comprised the following regimens: (1) NLA: 7.1 mg droperidol and 0.008 mg/kg body weight fentanyl, (2) IVA: 493.4 mg propofol and 0.004 mg/kg body weight fentanyl, and (3) BAL: 2.6 mg droperidol and 0.004 mg/kg body weight fentanyl with 0.4 vol.% isoflurane. With respect to anaesthetic risk, the following reactions were observed: the use of NLA led to a high incidence of tachycardia (P = 0.001), arrhythmias (P = 0.05), and hypertensive reactions (P = 0.001), whereas in the IVA group only hypotension (P = 0.0001) occurred. However, after the use of BAL none of the aforementioned complications were detectable to any considerable degree. Similarly, patients who had cardiac disease showed greater IEC changes after the use of NLA than after BAL or IVA (P = 0.02) (Tables 1 and 2). The heart rates and blood pressures during BAL and IVA were extremely stable, and therefore, vasoactive therapy was required considerably less in comparison to NLA (P = 0.001) (Table 4). Recovery after the use of IVA was strikingly rapid: the patient's responsiveness, orientation, and ability to concentrate was significantly better than after the other anaesthetic regimen (P = 0.01) (Table 5). With regard to the typical discomforts after anaesthesia, IVA was highly superior to BAL and NLA: nausea (P = 0.0003) and retching (P = 0.03) hardly ever occurred (Table 6). Due to the tolerable manner of waking up and rapid return of orientation and the ability to concentrate, IVA was highly favoured by the patients (P = < 0.01) (Table 7). CONCLUSION. The present results show clear clinical advantages of BAL and IVA in contrast to neuroleptanaesthesia. Due to the very low incidence of side effects such as nausea and vomiting IVA was highly recommended by the patients, at least in part because of the rapid recovery time.

Adult↗
PubMed1995

Pentamidine does not interfere with nitrite formation in activated RAW 264.7 macrophages but inhibits constitutive brain nitric oxide synthase.

Pentamidine effects on the interferon-gamma- or interferon-gamma plus bacterial lipopolysaccharide-induction of nitric oxide synthase in the macrophage cell line RAW 264.7, determined by measuring nitrite release into culture supernatants, were investigated. At concentrations above 10 microM, pentamidine caused visible toxic effects including cell lysis which also was assessed by measuring lactic dehydrogenase release. A progressive inhibitory effect of pentamidine could not be clearly dissociated from these toxic and lytic effects which were extensive at 100 microM. At 1 microM pentamidine, the dose response dependence of nitrite formation on interferon-gamma was not affected. Tumor necrosis factor-alpha caused some enhancement of interferon-gamma-induced nitrite release only at high doses of 100 and 10,000 unit/ml. Pentamidine had no effect on isolated inducible nitric oxide synthase from RAW 264.7 cells but inhibited the constitutive enzyme from pork cerebellum non-competitively. The lack of any stimulatory effect of pentamidine on nitrite production in RAW 264.7 cells suggests that NOS induction and NO production by macrophages is not the mechanism of the antimicrobial effects of this drug.

Animals↗
PubMed1995

To use or to refuse cocaine--the deciding factors.

Two types of narratives were obtained from 35 cocaine-addicted patients: narratives about using cocaine and narratives about not using cocaine. The most prevalent factors in using cocaine were (a) having enough money, (b) wish to end physical/emotional pain, and (c) wish/decision to use. The factors in narratives about not using cocaine were (a) patient arranged conditions to be nonstimulating for using cocaine, (b) recognition of bad consequences, and (c) wish/decision not to use. It is clear in both the cocaine-using episodes and not-using episodes that the patient's wish/decision is important. The conditions for using cocaine tended to be more external, whereas those for not using tended to be more internal. Similar conditions were found by a questionnaire method. A major treatment implication of these findings is that the focus of therapy can be directed to planning strategies to minimize influence of the external factors and to rehearse strategies to prepare for situations involving cues that influence use of cocaine.

Adult↗
PubMed1995

Systemic and cerebral kinetics of 16 alpha [18F]fluoro-17 beta-estradiol: a ligand for the in vivo assessment of estrogen receptor binding parameters.

Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha [18F]fluoro-17 beta-estradiol ([18F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [18F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [18F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [18F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [18F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [18F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [18F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus.

Animals↗
PubMed1995

Characterization of neuronal amino acid transporters: uptake of nitric oxide synthase inhibitors and implication for their biological effects.

In the present study we investigated uptake of the nitric oxide (NO) synthase inhibitors NG-methyl-L-arginine and NG-nitro-L-arginine by the mouse neuroblastoma x rat glioma hybrid cell line NG108-15. Uptake of NG-methyl-L-arginine was characterized by biphasic kinetics (Km1 = 8 mumol/L, Vmax1 = 0.09 nmol x mg-1 x min-1; Km2 = 229 mumol/L, Vmax2 = 2.9 nmol x mg-1 x min-1) and was inhibited by basic but not by neutral amino acids. Uptake of NG-nitro-L-arginine followed Michaelis-Menten kinetics (Km = 265 mumol/L, Vmax = 12.8 +/- 0.86 nmol x mg-1 x min-1) and was selectively inhibited by aromatic and branched chain amino acids. Further characterization of the transport systems revealed that uptake of NG-methyl-L-arginine is mediated by system y+, whereas systems L and T account for the transport of NG-nitro-L-arginine. In agreement with these data on uptake of the inhibitors, L-lysine and L-ornithine antagonized the inhibitory effects of NG-methyl-L-arginine on bradykinin-induced intracellular cyclic GMP accumulation, whereas L-tryptophan, L-phenylalanine, and L-leucine interfered with the effects of NG-nitro-L-arginine. These data suggest that rates of uptake are limiting for the biological effects of NO synthase inhibitors.

Amino Acid Oxidoreductases↗