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Biomedical subjects

A Markus

Publications and source records attributed to A Markus.

At least 55 records · Page 3Linked to original sources

Antibacterial activities in vitro and in vivo and pharmacokinetics of cefquinome (HR 111V), a new broad-spectrum cephalosporin.

Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3 h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.

Animals↗

Comparative chemotherapeutic activity of cefpirome and imipenem in experimental infections.

In systemic and local infections, the therapeutic efficacy of cefpirome was compared to that of imipenem and cefotaxime. Murine septicemia induced with methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains responded well to cefpirome and imipenem therapy, the ED50 values ranged from 0.8 to 28.40 mg/kg and 0.5 to 15.58 mg/kg, respectively. The carbapenem also displayed high efficacy against Enterococci and was more potent than cefpirome. Cefotaxime, however, exhibited lower activity or proved to be inactive against these strains. With ED50 values of 0.03 to 31.33 mg/kg, cefpirome was the most active of the three antibiotics in protecting mice challenged with Enterobacteriaceae. The corresponding ED50 values of imipenem and cefotaxime ranged from 0.72 to 70.95 mg/kg and 0.06 to 66.30 mg/kg, respectively. Despite distinctly lower in vitro activity against the infecting organism, cefpirome showed efficacy similar to imipenem in the treatment of subcutaneous S. aureus abscesses in mice. It was more effective than imipenem and cefotaxime against experimental Klebsiella pneumonia in mice and the Escherichia coli infected granuloma pouch in rats.

Abscess↗

Neurosis or psychosis?

The management of patients who attend the surgery requesting psychotropic medication is complicated by the inadequate classification of neuroses and the difficulty in distinguishing between neurotic and psychotic depression. Moreover, patients have lives to lead and know that there is treatment available as they have often been given tablets before.

Adult↗

Purification and some properties of component B of the 4-chlorophenylacetate 3,4-dioxygenase from Pseudomonas species strain CBS 3.

4-Chlorophenylacetate 3,4-dioxygenase system from Pseudomonas sp. CBS 3 consists of two protein components, a red-brown iron-sulfur protein (component A) which functions as dioxygenase and an orange-colored reductase (component B). Component B was purified by a five-step procedure. Criterion of purity was sodium dodecyl sulfate-polyacrylamide gel electrophoresis, which also showed that the protein consists of one polypeptide species with a molecular weight of 35,000. With gel chromatography on Sephadex G-100 also, a molecular weight of 35,000 was found for the native enzyme, suggesting a monomeric structure for the reductase enzyme. The isoelectric point was determined as pH 4.8. The visible absorption spectrum of the homogeneous protein exhibits maxima at 336, 394, and 458 nm. One mol of FMN, 2.1 mol of iron, and 1.7 mol of acid-labile sulfide were found in one mol of component B. The EPR-spectrum of the reduced form of the enzyme (with NADH) showed two types of signals. The signal at g values of 2.03, 1.94, and 1.90 was assigned to an iron-sulfur cluster of the [2Fe-2S]-type. The properties of the other signal type at g = 2.004 are characteristic of flavosemiquinone radical which does not show coupling to an other paramagnetic center. The apparent Km values for 2,6-dichlorophenolindophenol, cytochrome c, and NADH were calculated from Lineweaver-Burk plots as 6.3, 2.3, and 32 microM, respectively. Inhibitors of the reductase are metal-chelating reagents and sulfhydryl-inhibiting compounds. Component B reduces several redox compounds: 2,6-dichlorophenolindophenol, potassium hexacyanoferrat III, cytochrome c, methylene blue, and nitro blue tetrazolium.

2,6-Dichloroindophenol↗

Purification and some properties of component A of the 4-chlorophenylacetate 3,4-dioxygenase from Pseudomonas species strain CBS.

Pseudomonas sp. strain CBS 3 possesses a two-component enzyme system which converts 4-chlorophenylacetate to 3,4-dihydroxyphenylacetate by the incorporation of 2 atoms of molecular oxygen. Component A of this enzyme system was purified to homogeneity by a 5-step procedure. After the last purification step the enzyme was homogeneous in analytical and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of the native protein was determined to be 140,000 by Sephadex G-200 and 144,000 by analytical ultracentrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that component A consists of three identical subunits with a molecular weight determined to range between 46,000 and 52,000. The isoelectric point was estimated to be 5.0. Component A shows an intensive red-brown color, and in the oxidized state it exhibits a visible absorption spectrum with a maximum at 458 nm and a shoulder at 560 nm. By reduction with sodium dithionite a new peak with a maximum at 518-520 nm is observed. The enzyme contains iron (1.6-1.8 mol/subunit) and acid-labile sulfide (1.6-1.9 mol/subunit) which suggests that component A is an iron-sulfur protein.

Amino Acids↗

Family influences on the development of psychological problems in teenagers.

A study was designed to test the opinion that teenagers at risk of psychological disturbance can be identified on the basis of their family background. A copy of the general health questionnaire (28-question version) was sent to 322 17- and 18-year-olds registered with a semi-rural group practice. The records of all the 195 teenagers who replied, and those of their parents, brothers and sisters were examined and any record of chronic illness and psychological or social problems noted. Teenagers with family disruption, legal difficulties, parental marital problems or maternal psychiatric disorder recorded in the medical notes of their families were significantly more likely to have a high score on the general health questionnaire than those without such a record. Teenagers with high scores had attended the surgery more frequently during the previous year than those with low scores. Further work may enable more precise recording of family problems and enable a group at high risk of developing distressing psychological symptoms to be clearly identified. By early identification of this group, the general practitioner may be in a position either to prevent problems arising, or to intervene more effectively if a crisis develops.

Adolescent↗

Oxidation and dehalogenation of 4-chlorophenylacetate by a two-component enzyme system from Pseudomonas sp. strain CBS3.

In cell-free extracts from Pseudomonas sp. strain CBS3 the conversion of 4-chlorophenylacetate to 3,4-dihydroxyphenylacetate was demonstrated. By Sephacryl S-200 chromatography two protein fractions, A and B, were obtained which both were essential for enzyme activity. Fe2+ and NADH were cofactors of the reaction. NADPH also activated the enzyme, but less effectively than NADH. FAD had no influence on enzyme activity. 4-Hydroxyphenylacetate, 4-chloro-3-hydroxyphenylacetate, and 3-chloro-4-hydroxyphenylacetate were poor substrates for the enzyme, suggesting that these substances are not intermediates of the reaction. We therefore suggest that the reaction proceeds via a dioxygenated intermediate.

Cations, Divalent↗

A community study of diabetes in Oxfordshire.

A mailed questionnaire was used to identify people with diagnosed diabetes in a population of approximately 14,000. A response rate of 90 per cent was obtained and the prevalence of diabetes was found to be 0.8 per cent. The questionnaire method compared favourably with other methods of identifying diabetics in the area.Eighty-two diabetics were interviewed and examined for diabetic complications and 55 of these completed a questionnaire on their attitudes to diabetes and its care.The medical records of all 108 diabetics identified were examined. A greater proportion of patients who attended either a general practice mini-clinic or a hospital diabetic clinic had examination for complications recorded than patients attending their general practitioner in ordinary surgery time. Patients attending on demand were seen less often and had fewer observations recorded when they came.Comparison of measures of control between hospital and general practice patients showed that hospital patients tended to be more tightly controlled even though most were on insulin and likely to have more severe diabetes.Half of non-insulin diabetics and a quarter of those on insulin considered that their diabetes should be managed solely by their general practitioner.This was a pilot study and caution should be exercised in interpreting results from comparatively small numbers. The study has since been extended to a larger population. f10sl60

Adult↗

[Microbial degradation and 4-chlorophenylacetic acid. Chemical synthesis of 3-chloro-4-hydroxy-, 4-chloro-3-hydroxy- and 4-chloro-2-hydroxyphenylacetic acid (author's transl)].

Pseudomonas spec. CBS 3 converts 4-chlorophenylacetic acid partly into 3-chloro-4-hydroxy-, 4-chloro-3-hydroxy-, and 4-chloro-2-hydroxyphenylacetic acid by the action of monooxygenases. However, these compounds are not intermediates in the degradation of 4-chlorophenylacetic acid. Pseudomonas spec. CBS 3 is not able to grow with 3-chloro-4-hydroxy- and 4-chloro-3-hydroxyphenylacetic acid as sole carbon source. 4-Chloro-2-hydroxyphenylacetic acid is slowly degraded forming 4-chloro-2,3-dihydroxyphenylacetic acid. The actual degradation of 4-chlorophenylacetic acid seems to be initiated by the attack of a dioxygenase. The syntheses of 4-chloro-3-hydroxyphenylacetic acid and of 4-chloro-2-hydroxyphenylacetic acid are described.

Indicators and Reagents↗

Degradation of 4-chlorophenylacetic acid by a Pseudomonas species.

Pseudomonas sp. strain CBS3 was able to utilize 4-chlorophenylacetic acid as the sole source of carbon and energy. When this strain was grown with 4-chlorophenylacetic acid, homoprotocatechuic acid was found to be an intermediate which was further metabolized by the meta-cleavage pathway. Furthermore, three isomers of chlorohydroxyphenylacetic acid, two of them identified as 3-chloro-4-hydroxyphenylacetic acid and 4-chloro-3-hydroxyphenylacetic acid, were isolated from the culture medium. 4-Hydroxyphenylacetic acid was catabolized in a different manner by the glutathione-dependent homogentisate pathway. Degradation enzymes of both of these pathways were inducible.

3,4-Dihydroxyphenylacetic Acid↗

The children's hour: the State Children's Health Insurance Program.

The State Children's Health Insurance Program (CHIP) is the product of a series of policy and political compromises and generates numerous structural and policy issues for states. CHIP entitles states to federal financial aid to provide health assistance to targeted children, through Medicaid expansions, new program implementation, or a product of the two. States that elect to operate CHIP programs apart from Medicaid have enormous discretion under the law to determine how they will structure their programs, the services they will cover, the form that benefits will take, and the conditions of participation and consumer protections that will apply. Determining what approach to take, as well as how to respond to the choices posed by the statute, represents a major test of how states address the needs of children and families.

Aid to Families with Dependent Children↗