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Biomedical subjects

E Ludwig

Publications and source records attributed to E Ludwig.

At least 19 recordsLinked to original sources
PubMed1995

Angiotensin-converting enzyme gene polymorphism is associated with myocardial infarction but not with development of coronary stenosis.

BACKGROUND: Although both genetic and nongenetic factors contribute to the pathogenesis of coronary artery disease, the identification of specific genetic lesions has lagged behind the identification of critical environmental risk factors. A reported association between myocardial infarction (MI) and the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in European men suggests a critical role for this genomic region. However, the generality of this association remains to be determined. It also is not clear at what stage in disease progression the association with the ACE I/D polymorphism becomes important. METHODS AND RESULTS: We evaluated the ACE I/D polymorphism in patients who had undergone coronary angiography (402 men and 295 women) and in 203 representative control subjects. After polymerase chain reaction amplification, genotypes were determined by agarose gel sizing and by hybridization with allele-specific oligonucleotides. After patients were categorized by the degree of coronary artery stenosis and the occurrence of an MI, the distribution of ACE I/D genotypes was evaluated by log linear analysis. Patients were genetically representative of the regional population, and patients with > 60% stenosis of their coronary arteries had the same distribution of ACE I/D genotypes as did patients with < 10% stenosis. However, among patients with stenosis, the occurrence of an MI was significantly associated with the D allele in all patients (odds ratio [OR], 1.59; P = .002) and in men alone (OR, 1.63; P = .006). The lack of significance in women (OR, 1.40; P = .263) is probably due to the fact that only 36 women in the present study had experienced an MI. Furthermore, the association between MI and the ACE I/D polymorphism was independent of blood pressure, smoking habits, and body mass index. CONCLUSIONS: Segregation of the ACE I/D polymorphism is a pervasive genetic risk factor for MI in whites but has no evident effect on the events leading to stenosis of the coronary arteries. This suggests that risk of MI is influenced by two independent processes--atherogenesis that leads to coronary stenosis followed by conversion to MI. The renin-angiotensin system appears to confer significant risk of infarction by influencing the conversion to MI but has no apparent effect on the development of atherostenosis.

Aged↗
PubMed1995

Oxidation versus addition reactions of glutathione during the interactions with quinoid thioethers of 4-(dimethylamino)phenol.

4-(Dimethylamino)phenol (DMAP) is a potent cyanide antidote which forms many equivalents of ferrihemoglobin in vivo and in vitro. During this process formation of phenoxyl radicals was observed which are reduced by ferrohemoglobin, thereby sustaining a catalytic cycle of ferrihemoglobin formation, or which disproportionate to give the quinone imine of DMAP. In the presence of thiols, e.g., glutathione (GSH), formation of 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP), 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP), and 4-(dimethylamino)-2,3,6-tris(glutathion-S-yl)phenol (2,3,6-tris-GS-DMAP) was observed. While the trisubstituted glutathione conjugate is a stable end product, 2-GS-DMAP and 2,6-bis-GS-DMAP were still reactive and produced ferrihemoglobin. It is concluded that formation of polysubstituted DMAP thioethers is a result of sequential oxidation/addition reactions with quinoid intermediates. Formation of glutathione disulfide (GSSG) was minimal during the interaction of oxidized DMAP or 2-GS-DMAP with glutathione but became significant when oxidized 2,6-bis-GS-DMAP reacted with GSH. Thus it is conceivable that the bulky glutathione substituents in 2,6-bis-GS-DMAP render the addition of a third GSH molecule to the quinone imine derivative more difficult, and other reactions may get a chance. The reaction mechanism of GSSG formation has not been fully resolved, but a radical pathway mechanism involving thiyl radicals is proposed. Oxidation and addition reactions were also observed in the absence of oxygen when ferrihemoglobin served as oxidant. In the presence of oxygen, however, GSSG formation was increased, Partly due to hydrogen peroxide formation, partly due to an additional trapping reaction of the glutathione disulfide radical anion.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗
PubMed1995

Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Formation of a highly reactive cyclization product.

During ferrihemoglobin formation, 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, forms a quinoid compound that is prone to sequential oxidation/addition reactions. In human red cells and hemoglobin solutions fortified with glutathione, a transient adduct has been isolated and identified as 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP). This compound still formed ferrihemoglobin but differed from parent DMAP in that the reaction rate was roughly proportional to the oxygen concentration and exhibited a lag phase, pointing to a reactive autoxidation product. The compound was isolated and tentatively identified as an intramolecular cyclization product of 2-GS-DMAP. Formation of this product includes three reaction steps: (1) formation of a quinoid intermediate, (2) addition of the alpha-amino nitrogen atom of the glutamate residue to the aromatic ring, and (3) autoxidation of the cyclization product to give a highly reactive o-quinone imine. The isolated compound existed in two isomeric states (1H-NMR) which upon reduction could be separated by HPLC. The isolated reduced isomers mutually converted into each other. A model compound which was synthesized to mimic the most important structural features, 4-(dimethylamino)-6-[S-(2'-hydroxyethyl)-thio]-N-(2"-phenylethyl)-1,2- quinone imine, had a very similar visible spectum and exhibited an even higher ferrihemoglobin activity than the cyclization product. A similar phenomenon of intramolecular cyclization of a thioether of DMAP had been observed earlier: DMAP covalently bound to the SH groups of the beta-chains in hemoglobin formed a cross-link with the C-terminal histidine residue in the presence of oxygen but not in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗
PubMed1994

[Clinico-pharmacologic studies on pefloxacin].

The impact of liver impairment, renal insufficiency and age-related changes on the pharmacokinetics of pefloxacin was studied in 55 patients. The elderly patients were stratified into three age groups (61-70, 71-80 and above 81 years). The patients suffering from various infections were treated with oral or intravenous pefloxacin in a dose of 400 mg bid. Blood samples were withdrawn on the first and seventh day of therapy. The pharmacokinetics of pefloxacin was characterized by marked interindividual differences that became even more pronounced during multiple dosing. The elimination rate of pefloxacin during therapy slowed down, presumably due to its decreased metabolism. In elderly patients, the rate of cumulation is greater than in the young ones, but no significant differences could be detected among the elderly age-groups. Pefloxacin elimination also decreased in renal and hepatic impairment. There was no correlation between serum concentrations of pefloxacin and the development of adverse effects. In elderly subjects and in patients with renal or hepatic impairment, dose reduction might be considered. In mild or moderate infections or in urinary tract infections smaller doses of pefloxacin also could assure good therapeutic results. However, in severe infections especially caused by less susceptible pathogens, routine dose reduction is not recommended because of the significant interindividual differences in serum concentrations of pefloxacin.

Administration, Oral↗
PubMed1994

Analysis of free amino acids in green coffee beans. I. Determination of amino acids after precolumn derivatization using 9-fluorenylmethylchloroformate.

For the determination of free amino acids in green coffee beans, 9-fluorenylmethylchloroformate was applied successfully as the precolumn derivatization agent. The separation of the 27 free amino acids of green coffee as yet identified or quantitatively determined is almost complete. The paper describes in detail the conditions of extraction, derivatization and resolution and presents reproducible data of standard curves and of quantitative results. It has been demonstrated that by applying the extraction procedure described, 99.8% of the free amino acids detectable by this method are extracted. On principle, Arabica and Robusta coffees contain the same main and minor amino acids. It was possible for the first time to determine the free amino acids ornithine, beta-alanine and pipecolic acid quantitatively in Arabica and Robusta coffees as well as hydroxyproline in Arabica coffees.

Amino Acids↗
PubMed1994

The anti-tumour activity of ifosfamide on heterotransplanted testicular cancer cell lines remains unaltered by the uroprotector mesna.

Ifosfamide is clinically used in combination chemotherapy regimens for the treatment of patients with high-grade lymphomas, sarcomas and metastatic germ cell tumours. In order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients. Since an influence of mesna on ifosfamide anti-tumour activity is controversial, the current study has used xenografts from two human testicular cancer cell lines heterotransplanted into nude mice to study the anti-tumour activity of ifosfamide in combination with different dosages and schedules of mesna. In both human testicular cancer cell lines, H 12.1 and 2102 EP, ifosfamide demonstrated anti-tumour activity as a single agent. No reduction in ifosfamide activity was observed with the application of mesna at a dose range from 50% to 200% of the ifosfamide dose. Furthermore, the application of mesna before and 3 h after ifosfamide, a schedule used in many clinical protocols because of the short half life of mesna, not only maintained high ifosfamide anti-tumour activity but also seemed to be associated with the lower systemic and urothelial toxicity of ifosfamide therapy compared with ifosfamide given alone. In conclusion, the experimental in vivo system using human heterotransplanted testicular cancer cell lines confirms the significant anti-tumour activity of ifosfamide in malignant germ cell tumours and demonstrates that mesna does not impair ifosfamide anti-tumour activity in this model. These results are most likely transferable to the use of mesna in patients with metastatic testicular cancer.

Animals↗
PubMed1994

Structural requirements for the ferrihemoglobin-forming activity of glutathione S-conjugates of 4-dimethylaminophenol.

4-Dimethylaminophenol (DMAP) is a suitable cyanide antidote that rapidly forms ferrihemoglobin by catalytic transfer of electrons from ferrohemoglobin to oxygen. Deleterious methemoglobinemia, because of the catalytic cycling, is prevented by side reactions of oxidized DMAP with thiols, particularly with glutathione (GSH). In human red cells, both in vitro and in vivo, the formation of a transient bis-glutathione and a stable tris-glutathione adduct was observed. To investigate the reactivity of GSH adducts of DMAP, we synthesized various thioethers by oxidizing DMAP with PbO2 in 0.1 M sulfuric acid followed by reaction with GSH. The following compounds were isolated and characterized by 1H-NMR spectroscopy and determination of the pK values: 4-dimethylamino-2-(glutathione-S-yl)-phenol (2-GS-DMAP), 4-dimethylamino-3-(glutathione-S-yl)-phenol (3-GS-DMAP), 4-dimethylamino-2,5-bis(glutathione-S-yl)-phenol (2,5-bis GS-DMAP), 4-dimethylamino-2,6-bis(glutathione-S-yl)-phenol (2,6-bis GS-DMAP), and 4-dimethylamino-2,3,6-tris(glutathione-S-yl)-phenol (2,3,6-tris GS-DMAP). Ferrihemoglobin-forming activity was investigated with oxyhemoglobin, alkylated with N-ethylmaleimide (Hb-NES) to prevent binding of oxidized compounds to the protein SH groups. DMAP, 2,6-bis-GS-DMAP, and 2-GS-DMAP (0.1 mM each) completely oxidized Hb-NES (0.6 mM) in a decreasing order of activity (pH 7.4, 37 degrees C, air); the other derivatives were quite inactive. The same thioether reactivity was observed during autoxidation. Ferrihemoglobin formation by the reactive thioethers was greatly enhanced when the oxygen tension was increased from 2 to 100%. In contrast, variation of the oxygen tension had only marginal effects on the activity of DMAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophenols↗
PubMed1993

Response of left ventricular diastolic filling to graded exercise relative to the lactate threshold.

During incremental exercise, the left ventricular ejection fraction increases up to the intensity of the anaerobic threshold and tends to level off at higher exercise intensities. Since there is a correlation between the response of peak filling rate and ejection fraction to exercise, this study was conducted to determine whether the response of left ventricular diastolic function is similar to the response of systolic function relative to lactate threshold. Twelve healthy men performed two exercise tests on a cycle ergometer. In the first test, lactate threshold and maximal power output were determined. In the second exercise test, gated radionuclide ventriculography was performed at rest, at the lactate threshold intensity, and at peak exercise to measure ejection fraction and peak filling rate. Ejection fraction increased significantly from rest [mean (SD): 62 (5)%] to lactate threshold [76 (7)%] and did not change significantly from lactate threshold to peak exercise [77 (7)%]. Likewise, peak filling rate (normalized for stroke counts) increased from resting [6.1 (0.9) VS.s-1] to lactate threshold [9.4 (1.8) VS.s-1] and did not change significantly from lactate threshold to peak exercise [9.6 (2.9) VS.s-1]. There was no correlation between the change in peak filling rate and the change in ejection fraction from rest to lactate threshold. Thus, during incremental exercise, left ventricular diastolic function responds qualitatively similar to systolic function.

Adult↗
PubMed1993

Clinical observations with Péflacine.

The results of our study prove--incongruency with data in references--that pefloxacin, Pèflacine (EGIS-Rhône-Poulenc-Rorer) can be successfully used in the treatment of severe, medium severity infections acquired in hospitals. Our observations refer to urinary tract, hepatic-biliary tract, and lower respiratory tract infections. Differences were not found between the effectivity of oral and intravenous drug doses. Side-effects were observed in a relatively low number of cases, in 10% of the patients. On the basis of our observations pefloxacin seems to be an effective drug which can be used safely.

Administration, Oral↗
PubMed1991

[The determination of protein hydrophobicity. 1. Determination of the hydrophobicity of selected cereal and milk proteins using their sodium dodecyl sulfate binding capacities].

The sodium dodecylsulphate (SDS) binding capacities of secalin, gliadin and gluten in the presence of a very low SDS concentration were determined and compared to the SDS binding capacities of bovine serum albumin (BSA), beta-lactoglobulin, ovalbumin und beta-casein. The SDS binding capacities of endosperm proteins determined in phosphate buffer (pH 6.0) are very low. Only 0.6 microgram .. 0.8 microgram SDS were bound to 500 micrograms of the proteins. This low SDS binding capacities do not correlate with the expected hydrophobicity of these proteins. In comparison, 500 micrograms of ovalbumin, beta-lactoglobulin and BSA each bind 0.5, 5.9 and 13.5 micrograms SDS, respectively. According to literature the SDS binding capacities of these proteins are in correlation with the surface hydrophobicity determined with cis-parinaric acid using the fluorescence probe method. The SDS binding capacities of endosperm proteins increased in the presence of 0.1 N acetic acid and consequently 6.2 micrograms .. 6.9 micrograms SDS were bound to 500 micrograms of the corresponding proteins. beta-casein described as a highly hydrophobic protein binds only 0.9 micrograms SDS to 500 micrograms of it in phosphate puffer (pH 6.0) and 1.2 micrograms SDS in 0.1 N acetic acid, respectively.

Chemical Phenomena↗
PubMed1991

[The determination of protein hydrophobicity. 2. Determination of the of protein binding of sodium dodecyl sulfate with the use of the ultracentrifuge].

The interaction between sodium dodecylsulphate (SDS) and the proteins bovine serum albumin (BSA) and ovalbumin, respectively, was studied using a synthetic boundary cell of an ultracentrifuge. A method for the determination of protein-bound SDS is described. The SDS binding capacity of BSA is found to be 250 +/- 50 micrograms SDS per 500 micrograms of BSA. The amount of SDS bound by ovalbumin is so low that the procedure cannot be recommended for this protein.

Ovalbumin↗
PubMed1989

High-frequency jet ventilation during oleic-acid induced pulmonary oedema.

In oleic acid-induced pulmonary oedema (OAPO) sequential intrapulmonary fluid accumulation occurs leading to different expiratory flow pattern in dependent lung regions. The potential effects on efficacy of high-frequency jet ventilation (HFJV, f = 3 Hz, I: E = 0.43, FiO2 = 0.4) were studied and compared with continuous positive pressure ventilation (CPPV, f = 12-18/min, I:E = 0.5, TV = 12 ml/kg, PEEP = 0.5 kPa, FiO2 = 0.4) in a dog model of OAPO. In the control state (lung-healthy dogs), 15 min after oleic acid lung injury (interstitial oedema, period I) and 60 min after onset of OAPO (alveolar oedema, period II), gas exchange, lung volumes, compliance, resistance and haemodynamics were measured. The course of lung oedema was determined indirectly by means of washout curves of helium (foreign gas bolus-test, FGB) and nitrogen (single breath-test for oxygen, SBO2). During control, there were no significant differences between the HFJV-group (n = 7) and the CPPV-group (n = 6) by virtue of gas exchange, lung volumes and haemodynamics. During period I, PaO2 decreased significantly both with HFJV (p less than 0.01) and CPPV (p less than 0.05), being lower in the HFJV-group (p less than 0.05). PaCO2, pulmonary and haemodynamic parameters were unchanged. Onset of phase IV of the alveolar plateau (closing volume CV) occurred significantly earlier (p less than 0.05) in all animals. Impaired ventilation of dependent lung regions, increased maldistribution of intrapulmonary gas and VA/Q-mismatching may be the underlying mechanisms for lower efficacy of HFJV during interstitial lung oedema. In period II, pulmonary and cardiocirculatory parameters had changed significantly in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The effect of ciprofloxacin on antipyrine metabolism.

The effect of multiple-dose ciprofloxacin on antipyrine metabolism was studied in patients suffering from bacterial infections. The patients were given antipyrine 15 mg/kg intravenously before and after ciprofloxacin treatment. The dosage of ciprofloxacin was 500 mg bd by mouth for 8-10 days. Blood samples were taken at 0, 2, 4, 6, 10 h. Antipyrine total clearance was significantly decreased after ciprofloxacin treatment (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg): elimination rate constants for antipyrine were decreased in all patients after ciprofloxacin, whereas no change in volume of distribution was observed. The average half-life of antipyrine was increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h. In two males with advanced chronic hepatic failure the antipyrine half-lives were extremely prolonged. Our results support the hypothesis that ciprofloxacin inhibits intrinsic hepatic drug-metabolizing capacity and may be a source of clinically important drug interactions, particularly in patients with liver disease.

Adult↗
PubMed1988

Pharmacokinetics of cefotaxime and desacetylcefotaxime in elderly patients.

This study was undertaken to determine the effect of age on the pharmacokinetics of cefotaxime and desacetylcefotaxime after intravenous administration of 1 g cefotaxime. 30 elderly patients suffering from acute infection were enrolled in the study. They were divided into 3 subgroups (group I aged 60 to 70 years, group II aged 71 to 80 years, group III aged over 80 years) with 5 men and 5 women in each. The elimination of cefotaxime in patients aged between 60 and 80 years was slightly slower than that in young people: elimination half-lives (in men and women, respectively) in group I were 1.2 and 1.58 hours, in group II, 1.45 and 1.57 hours and in group III, 2.56 and 2.59 hours. The change in elimination of desacetylcefotaxime was similar to that of cefotaxime, but less marked. The slower elimination of cefotaxime in patients over 80 years of age may allow reduction in the dose without jeopardizing the efficacy of therapy, whereas in patients under 80 years of age the normal dosage is required.

Age Factors↗
PubMed1987

[Pili canaliculi, a form of uncombable hair].

Two further cases of the hair abnormality described in 1973 by Dupré et al. as "cheveux incoiffables" and later (1978) termed pili trianguli and canaliculi are reported. This hair abnormality--a distinct anomaly without the associated physical or mental abnormalities encountered in other cases of uncombable hair--starts in the first year of life, tending to improve or to become entirely normal with age. The morphological characteristics of such hairs are grooves along the hairshaft (demonstrable only by scanning electron microscopy), resulting in triangular, reniform, or irregular cross-sections. Of the various terms used to designate the condition, that proposed by Ferrando et al. (1980) pili canaliculi, appears to be the most appropriate.

Child, Preschool↗