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Biomedical subjects

R Wise

Publications and source records attributed to R Wise.

At least 73 records · Page 4Linked to original sources
PubMed2000

Preface.

Although the clinical presentation and the treatment of lower urinary tract infection (UTI) have changed little in the 60 to 70 years of the 'antibiotic era', uropathogenic bacteria have not been slow to respond to the selecting pressure of antimicrobials. This is because such infections are common. Approximately 3% of all consultations made to general practitioners are for symptoms of UTI and approximately 12-20% of all antibiotic prescriptions are for this indication. Between one-quarter and one-half of all women experience a UTI at some time. The problem, therefore, is a considerable one and warrants reevaluation. This supplement is based upon papers presented at a meeting held in March 2000 in Vienna, Austria and sponsored by Leo Pharmaceutical Laboratories. It draws together the current views on the diagnosis and the treatment of UTIs at a time when the disease-causing microorganisms are most certainly changing. Antibiotic resistance to commonly used agents, such as trimethoprim and ampicillin, often now exceeds 30-50%. The clinician may be tempted to choose an agent such as a fluoroquinolone for the treatment of this disease, yet it is known that fluoroquinolone resistance can develop rapidly. Views on the length of treatment have also changed over the years and a 3 day regimen is usually now advocated. Pivmecillinam, which is hydrolysed to mecillinam after absorption, has a novel mode of action, rapid bacterial cell penetration and lower affinity for common beta-lactamases. Its spectrum of activity and good safety profile make it an ideal candidate for the treatment of this common condition. Experience in several countries over many years confirms this assessment and it may be time to reconsider the potential role of pivmecillinam in the treatment of UTIs. The Editors would like to thank Inge Boe and Paul Menday of Leo Laboratories for their untiring support and assistance in the preparation of this supplement.

Journal Article↗
PubMed2000

New restraint standards will change your practice.

New restraints and seclusion standards from Joint Commission on Accreditation of Healthcare Organizations require you to use restraints or seclusion only for emergency situations when there is imminent risk of physical harm to a patient or others. The standards will be scored for compliance in January 2001 and will not be capped (a sliding scale scoring system usually used for several months after new standards are introduced). Document that alternative measures, such as trying to contact family members, were considered before restraints were used. The need for restraint must be described by behavior, not diagnosis.

Emergency Service, Hospital↗
PubMed1999

Production of type 2 cytokines by CD8+ lung cells is associated with greater decline in pulmonary function in patients with systemic sclerosis.

OBJECTIVE: This study addresses the hypothesis that a profibrotic pattern of cytokines is produced in the lungs of patients with systemic sclerosis (SSc) and causes fibrosis. METHODS: Using a reverse transcriptase-polymerase chain reaction technique, interleukin-4 (IL-4), IL-5, and interferon-gamma (IFNgamma) messenger RNA (mRNA) were measured in unseparated CD8+ and CD4+ bronchoalveolar lavage (BAL) cells from SSc patients and healthy controls. To confirm the results, CD8+ T cells were cloned from BAL fluids, and the pattern of cytokine mRNA made by these cells was determined. Serial pulmonary function tests were done. RESULTS: BAL cells from healthy controls made IFNgamma mRNA, with no or little IL-4 or IL-5 mRNA. In contrast, BAL cells from the majority of SSc patients made IL-4 and/or IL-5 mRNA, with or without approximately equal amounts of IFNgamma mRNA. This pattern of cytokines was made by CD8+ T cells, which were increased in the lungs of these SSc patients. Patients whose BAL cells made this type 2 pattern of cytokine mRNA had a significant decline in forced vital capacity over time after the BAL, whereas patients whose BAL cells made IFNgamma mRNA alone did not. Both wild-type and an alternative splice variant of IL-4 mRNA were increased in BAL cells from SSc patients. Both forms of IL-4 stimulated alpha2(I) collagen mRNA in human dermal and lung fibroblasts. CONCLUSION: The type 2 pattern of cytokine mRNA produced by BAL cells from SSc patients differs from unopposed IFNgamma production found in healthy BAL cells. This production of type 2 cytokine mRNA by CD8+ T cells is associated with a significant decline in lung function over time, which suggests a pathologic role for these T cells in interstitial fibrosis in SSc.

Adolescent↗
PubMed1999

Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract.

Pharmacokinetic and pharmacodynamic features are important predictors of the therapeutic efficacy of an antibiotic. In respiratory tract infection, study of the clinical implication of pharmacodynamic features is complicated as infection occurs at several distinct sites. To ensure microbiological efficacy, antibiotics should not only be active against common respiratory pathogens but should also penetrate to the sites of infection. The newer fluoroquinolones combine good activity against Gram-negative and "atypical" organisms with extended Gram-positive activity, and are unaffected by penicillin susceptibility status and beta-lactamase production. Long terminal half-lives allow once-or twice-daily dosing, and a concentration in lung tissue at levels many times higher than is observed in the serum. Although the benefit of antibiotics in some lower respiratory tract infections has been questioned, they have proved effective in community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease. Early studies of oral fluoroquinolones versus intravenous or oral treatment with one or more agents in community-acquired pneumonia have shown promise. Although resistance is a potential problem with increased fluoroquinolone use, its rapid development is not anticipated. In conclusion, the broad-spectrum antimicrobial activity, tissue distribution and safety profile of fluoroquinolones suggest that they have a place in respiratory tract infection.

Anti-Infective Agents↗
PubMed1999

A thermal vascular test for distinguishing between patients with Raynaud's phenomenon and healthy controls. Raynaud's Treatment Study Investigators.

This study tested the reliability and validity of a diagnostic thermal vascular test (TVT) for patients with Raynaud's Phenomenon (RP). The TVT examined digital blood pressure responses to combined cooling and occlusion and was developed as part of the Raynaud's Treatment Study, a multicenter clinical trial comparing the efficacy of biofeedback and pharmacological treatment. A computerized system permitted efficient, accurate, and uniform testing at different geographical sites. A comparison of 199 patients with RP and 52 healthy controls is reported. The TVT showed a sensitivity of 79% and a specificity of 88%. Test-retest reliability was acceptable (r = .80). Addition of a psychological challenge failed to improve the discrimination between patients with RP and controls. The TVT separated patients with RP and controls as well as or better than existing tests and did so with enhanced ease of operation.

Diagnosis, Differential↗
PubMed1999

The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy.

The concentrations of clinafloxacin were measured in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid after single 200 mg oral doses of clinafloxacin had been administered to 15 subjects who were undergoing bronchoscopy. Concentrations were measured using a microbiological assay method. Mean concentrations in serum, bronchial mucosa, alveolar macrophages and epithelial lining fluid at a mean of 1.27 h post-dose were 1.54, 2.65, 15.60 and 2.71 mg/L respectively. These site concentrations exceeded the MIC90 for common respiratory pathogens and indicate that clinafloxacin is likely to be effective in the treatment of a wide range of respiratory tract infections.

Administration, Oral↗
PubMed1999

Antimicrobial resistance in gram-positive pathogens isolated in the UK between October 1996 and January 1997.

Antimicrobial resistance in gram-positive pathogens from 30 centres in the UK (ten Teaching, ten Associate Teaching and ten District General Hospitals) was studied over a 4 month period between October 1996 and January 1997. High-level resistance (HLR) and low-level resistance (LLR) to penicillin amongst pneumococci was 3.3% and 3.4%, respectively. However, considerable variation in resistance rates was observed depending on geographical location (LLR range 0-15.4% and HLR range 0-30.8%). Considerable variation in resistance rates was also observed for Staphylococcus aureus to methicillin, with rates ranging from 0% to 56.7% depending on locality. Using conventional MIC methodology, none of the isolates of S. aureus was considered as having reduced sensitivity to vancomycin. However, eight isolates grew on Brain Heart Infusion Agar containing vancomycin (4 mg/L) after prolonged incubation and are therefore worthy of further investigation by electron microscopy. With Enterococcus faecalis, resistance rates were similar between the three types of hospital and only four isolates were considered resistant to glycopeptide antibiotics (one vanA and three vanB phenotype).

Anti-Bacterial Agents↗
PubMed1999

Bactericidal properties of moxifloxacin and post-antibiotic effect.

The time-kill kinetics and post-antibiotic effect (PAE) of moxifloxacin were studied for strains of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Staphylococcus aureus and Escherichia coli. Moxifloxacin had a bactericidal effect against all strains tested, with the least rapid bactericidal effect being against S. pyogenes and the most rapid effect against S. aureus and E. coli. The PAE of moxifloxacin was similar to that of other fluoroquinolones and increased with increasing concentration. No association was found between the bactericidal effect of moxifloxacin and the duration of PAE. Gram-positive and gram-negative organisms were also exposed to concentrations of moxifloxacin, sparfloxacin and amoxycillin that simulated the drug concentrations obtained in human serum after standard oral dosing schedules. Simulation of moxifloxacin concentrations in human serum reduced viable counts more effectively and more rapidly than shown in time-kill experiments; in contrast, sparfloxacin and amoxycillin were less effective than when constant concentrations of these antibacterials were used.

Anti-Infective Agents↗
PubMed1999

The in-vitro activity and tentative breakpoint of gemifloxacin, a new fluoroquinolone.

The in-vitro activity of gemifloxacin, a new fluoroquinolone, against a wide range (c. 700) of recent clinical isolates, was compared with that of three other fluoroquinolones and other relevant agents. Gemifloxacin inhibited 90% of the Enterobacteriaceae strains at 0.5 mg/L or less, exceptions being Serratia spp. (MIC(90) 1 mg/L) and strains possessing a putative mechanism of resistance to fluoroquinolones. Ninety per cent of Pseudomonas aeruginosa were inhibited by 4 mg/L. Gemifloxacin had good activity against respiratory pathogens, with 90% of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis being inhibited by 0.06 mg/L or less. Staphylococcus aureus (MSSA) were highly susceptible (MIC(90) 0.06 mg/L) but MRSA less susceptible (MIC(90) 8 mg/L) to gemifloxacin. Enterococcus spp. were markedly more susceptible to the study agent than to ciprofloxacin. Gemifloxacin showed good activity against Bacteroides fragilis (MIC(90) 0.5 mg/L) and anaerobic cocci. A tentative in-vitro breakpoint of 0.5 mg/L was studied using a 1 microg disc content for all genera except Pseudomonas where a 5 microg disc content was employed. The false sensitivity reporting rate was 0.5% and false resistance rate was 6.0%, which was considered acceptable. In conclusion, gemifloxacin is a highly active fluoroquinolone that should prove clinically useful in the treatment of a wide range of infections. Susceptibility testing criteria have been developed that should prove robust in a clinical laboratory.

Anti-Bacterial Agents↗
PubMed1999

A study to determine the pharmacokinetics and inflammatory fluid penetration of gatifloxacin following a single oral dose.

A single 400 mg oral dose of gatifloxacin was given to each of nine healthy male volunteers and the concentrations of the drug in plasma, cantharidine-induced inflammatory fluid and urine were measured over the following 24 h. The mean peak concentration in plasma of 4. 1 mg/L was attained at a mean time of 1.8 h post dose. The mean peak concentration in inflammatory fluid was 3.6 mg/L and was attained at a mean time of 4.2 h post dose. The mean plasma elimination half-life of gatifloxacin was 6.8 h and that in inflammatory fluid was 7.2 h. The mean penetration into the inflammatory fluid was 117%. Recovery of drug from urine during the first 24 h post dose was 65% of that administered. Our data suggest that gatifloxacin dosed at 400 mg od should be adequate to treat systemic infections caused by most bacterial species.

Administration, Oral↗
PubMed1999

Tentative minimum inhibitory concentration and zone diameter breakpoints for moxifloxacin using BSAC criteria.

Tentative MIC and zone diameter breakpoints were determined for moxifloxacin using BSAC criteria. An MIC breakpoint of < or =1 mg/L, denoting sensitivity, is suggested for Enterobacteriaceae, staphylococci, haemophili, moraxellae, pneumococci and enterococci. For pseudomonads high and low breakpoints of 4 mg/L and 1 mg/L are suggested to allow for an intermediate category of sensitivity. A 1 microg moxifloxacin disc content is suggested for testing all of the organisms previously mentioned, except pseudomonads, for which a 5 microg disc is needed to discriminate between the intermediate and sensitive populations. Corresponding zone diameter breakpoints for a 1 microg disc are > or = 20 mm for Enterobacteriaceae and staphylococci, 18 mm for the respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and 15 mm for enterococci. For Pseudomonas aeruginosa with a 5 microg disc, three bands are suggested for interpretation, that of > or = 25 mm (sensitive), 18-24 mm (intermediate) and < or = 17 mm (resistant).

Anti-Infective Agents↗
PubMed1999

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

Anti-Infective Agents↗
PubMed1999

Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae.

An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.

Amino Acid Sequence↗
PubMed1999

Pharmacokinetics and inflammatory-fluid penetration of moxifloxacin following oral or intravenous administration.

A single 400-mg oral or intravenous (i.v.) dose of moxifloxacin was given to each of eight healthy male volunteers, and 6 weeks later the dose was administered by the other route. The concentrations of the drug in plasma, cantharidin-induced inflammatory fluid, and urine were measured over the subsequent 24 h. The mean maximum concentrations observed in plasma were 4.98 microg/ml after oral dosing and 5.09 microg/ml after i.v. dosing. The mean maximum concentrations attained in the inflammatory fluid were 2.62 and 3.23 microg/ml, respectively. The mean elimination half-lives from plasma were 8.32 and 8.17 h, respectively. The overall penetration into the inflammatory fluid was 103.4 and 104.2%. Over 24 h 15% of the drug was recovered in the urine when administered by either route.

Administration, Oral↗
PubMed1999

Study to assess the reliability of a disc diffusion method for determining the sensitivity of gram-positive pathogens to dalfopristin/quinupristin.

A standardized method of disc testing the sensitivity of gram-positive pathogens to dalfopristin/quinupristin was developed, and then 'field tested' in ten centres in the UK. For a 15 microg disc, zone diameter breakpoints of 20 mm and 15 mm are suggested when organisms are tested on Iso-Sensitest agar and Iso-Sensitest agar supplemented with 5% whole horse blood, respectively.

Animals↗
PubMed1998

Early and late weight gain following smoking cessation in the Lung Health Study.

The authors examine weight gains associated with smoking cessation in the Lung Health Study (1986-1994) over a 5-year follow-up period. A cohort of 5,887 male and female smokers in the United States and Canada, aged 35-60 years, were randomized to either smoking intervention or usual care. Among participants who achieved sustained quitting for 5 years, women gained a mean of 5.2 (standard error, 5.0) kg in year 1 and a mean of 3.4 (standard error, 5.5) kg in years 1-5. Men gained a mean of 4.9 (standard error, 4.9) kg in year 1 and a mean of 2.6 (standard error, 5.8) kg in years 1-5. In regression analyses, smoking-change variables were the most potent predictors of weight change. Participants going from smoking to quit-smoking in a given year had mean weight gains of 2.95 kg/year (3.61%) in men and 3.09 kg/year (4.69%) in women. Over 5 years, 33% of sustained quitters gained > or = 10 kg compared with 6% of continuing smokers. Also among sustained quitters, 7.6% of men and 19.1% of women gained > or = 20% of baseline weight; 60% of the gain occurred in year 1, although significant weight gains continued through year 5. The average gains and the high proportions of sustained and intermittent quitters who gained excessive weight suggest the need for more effective early interventions that address both smoking cessation and weight control.

Adult↗