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Biomedical subjects

P G Higgins

Publications and source records attributed to P G Higgins.

At least 19 recordsLinked to original sources
PubMed2003

Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa.

The target enzymes GyrA and ParC and two efflux pump regulatory genes mexR and nfxB were analysed to determine changes associated with fluoroquinolone resistance in Pseudomonas aeruginosa. Both low- and high-level ciprofloxacin resistance was associated with a Thr-83Ile substitution in GyrA. A ParC Ser-80Leu substitution was found in highly resistant isolates in tandem with the Thr-83Ile substitution in GyrA. Mutations in the efflux regulatory genes were associated with resistance only when in tandem with a mutation in GyrA or ParC. These data show that the main mechanism of fluoroquinolone resistance in P. aeruginosa is mediated primarily through mutations in GyrA, and that mutations in ParC and the efflux regulatory genes are secondary.

Amino Acid Sequence↗
PubMed2003

Fluoroquinolones: structure and target sites.

The quinolones are a potent group of drugs that target the essential bacterial enzymes DNA gyrase and topoisomerase IV. DNA gyrase is the primary target of Gram negative organisms however, it is topoisomerase IV that is the primary target of Gram positive organisms. Within these enzymes is a highly conserved region centered round the active site where resistance mutations occur. These mutations are almost always identical, irrespective of organism. In spite of the homology of this region, amino acid sequence analysis shows that there are defined differences between the Gram groups, particularly in topoisomerase IV, and it is speculated that herein lies the origin of target preference. Since the first quinolone nalidixic acid was developed, the quinolones have undergone structural modifications, in particular the addition of a fluorine at position 6, to produce the fluoroquinolones. This has seen their potency and pharmakokinetic profile greatly increase. In vitro selection of resistance mutations has allowed the observation of how resistance is acquired and some of the modifications in newer fluoroquinolones have resulted in the shift of primary target from topoisomerase IV to gyrase with Gram positives. Curiously, purified topoisomerase IV is still more sensitive even if gyrase is the primary target. Gyrase remains the primary target for Gram negatives.

Amino Acid Sequence↗
PubMed2002

Activity of quinolones against gram-positive cocci: mechanisms of drug action and bacterial resistance.

The quinolones are a potent class of antimicrobial agents that target two essential enzymes of bacterial cells: DNA gyrase and topoisomerase IV. Resistance is mediated chiefly through stepwise mutations in the genes that encode these enzymes, leading to alterations of the target site. These mutations occur in an area called the "quinolone resistance determining region". In gram-positive organisms, mutations occur more often in topoisomerase IV than in DNA gyrase. This target preference appears to depend upon two factors: the species of organism and the selecting drug. Resistance can be enhanced by a decrease in intracellular drug concentration, which is mediated through efflux pumps. The newer generation of fluoroquinolones and non-fluorinated quinolones exhibits enhanced activity against gram-positive organisms compared to the older members of this drug class, although development of resistance to these drugs has been demonstrated in vitro. This review gives a chronological perspective of the literature on the action of DNA gyrase and topoisomerase IV and the mechanisms of resistance to quinolones in staphylococci, streptococci and enterococci.

Anti-Infective Agents↗
PubMed2000

Bactericidal and bacteriostatic activity of gemifloxacin against Acinetobacter spp. in vitro.

This study compared the in vitro bacteriostatic activity of gemifloxacin (SB-265805) and a panel of test antimicrobial agents against 100 clinical isolates of Acinetobacter spp. (47 Acinetobacter baumannii, 18 Acinetobacter anitratus, 18 Acinetobacter lwoffii, 13 Acinetobacter calcoaceticus and four other Acinetobacter spp.). Gemifloxacin (MIC(50/90) 0.06/16 mg/L) was more than eight-fold more potent than ciprofloxacin (0.5/>128 mg/L), two- to eight-fold more potent than grepafloxacin, moxifloxacin, levofloxacin, ofloxacin and gatifloxacin, and of similar potency to trovafloxacin and sparfloxacin. Cross-resistance was seen only within the quinolone group and did not extend to non-quinolone antimicrobials. The bactericidal activities of gemifloxacin and the six comparator quinolones were investigated by dose-response and time-kill studies against A. baumannii ATCC 19606 at their optimum bactericidal concentration (OBC) and at 4 x MIC. At the OBC there was no significant difference between the quinolones, but at 4 x MIC gemifloxacin showed superior activity, reducing the viable count by almost 2 log(10) in 30 min compared with a 1 log(10) reduction seen with the other drugs. This enhanced killing extended over 24 h, reducing cell numbers by >4 log(10). These data suggest that gemifloxacin has the potential to be of therapeutic value in the treatment of infection by Acinetobacter spp.

Acinetobacter↗
PubMed1999

Health practices of adult Hispanic women.

The purpose of this focused ethnography was to discover the patterns and variability of health practices used by Hispanic women aged 20-40 years. Seven adult Hispanic women from an urban New Mexico county were interviewed four to seven times each about their health practices. The women described their views of good health. They were aware of current health promotion practices such as good nutrition and exercise. They also practised safety measures for themselves and their families. These women did not report any information on specific cultural disease prevention behaviours and described few practices related to their Hispanic culture. A theme that also emerged from the data was an emphasis on the importance of spirituality and the integration of the spiritual dimension as important to healthy living. Implications for health care providers include knowing that urban adult Hispanic women are versed in contemporary health literature and take better care of their families than of themselves.

Adult↗
PubMed1995

Drug-taking behaviours of pregnant substance abusers in treatment.

The purpose of this research was twofold: to describe the types of drugs and alcohol abused by pregnant multisubstance abusers enrolled in a substance abuse and treatment programme, and to describe the types of changes in drug-taking behaviours during pregnancy. An exploratory study, including interviews and chart reviews, was conducted with 31 pregnant multisubstance abusers. Drug-taking behaviours, demographic factors of age, ethnicity, martial status, education, and pregnancy characteristics of gravida, living children, level of prenatal care and trimester of pregnancy were measured. Most of the women were in their Twenties, Hispanic, single and had some high school education. Most of the women were multiparas to grand multiparas, yet they had only one or two living children, and all were receiving prenatal care. Their self-reports were validated by urine screening. Generally, the women reported that they did change their drug-taking behaviours, and many women decreased their substance abuse.

Adolescent↗
PubMed1995

Changes in health behaviors made by pregnant substance users.

A descriptive survey was conducted with 31 pregnant women who were substance users enrolled in a perinatal treatment program. The purpose of the study was to determine the women's health behaviors by using open-ended questions. Most of the women were between 20 and 29 years of age, Hispanic, not married, unemployed, and had partial or completed high-school education. The women had multiple pregnancies with few living children. The majority of the women were 4 to 6 months pregnant and all had received prenatal care. The women made health behavior changes during pregnancy related to nutrition, substance use, self-care, exercise, lifestyle, and seeking counseling. Over 52% of the women reported they made these behavioral changes because they wanted a healthy baby.

Adolescent↗
PubMed1992

The common cold, pattern sensitivity and contrast sensitivity.

Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.

Adolescent↗
PubMed1992

Bronchial reactivity to histamine and bradykinin is unchanged after rhinovirus infection in normal subjects.

We investigated the effects of rhinovirus (RV) infection on airways reactivity. Twenty seven normal volunteers (11 atopic) were inoculated with RV 2 or RV EL. The provocative concentrations of histamine and bradykinin required to produce a 15% fall in the forced expiratory volume in one second (FEV1) (PC15FEV1) were measured before, 7 and 21 days after inoculation. Infection was determined by a fourfold rise in anti-viral antibody titre and by viral culture from nasal washings. Peak expiratory flow rate (PEF) was recorded three days before and for 21 days after inoculation. All subjects underwent the first two bronchial challenges, and 22 the third challenge. For the whole group and for atopic subjects, there were significant correlations between the PC15 values for bradykinin and histamine (r = 0.82 and r = 0.85, respectively). Twenty subjects were infected; six had clinical colds. For the 16 infected subjects who had all three challenges, the median (range) PC15FEV1 for the histamine challenges was 36 (0.89-64), 62 (1.5-64) and 34 (0.94-64) mg.ml-1, respectively, and 32 mg.ml-1 for each bradykinin challenge (range: 0.015-32, 0.088-32 and 0.033-32). There were no significant differences between study days for PC15FEV1 histamine or bradykinin for the whole group, the infected subjects, those with clinical colds or for those infected with either RV subtype. There was no significant change in mean daily PEF after viral infection. We conclude that airways reactivity to histamine and bradykinin is unchanged after experimental RV infection in normal volunteers.

Administration, Inhalation↗
PubMed1990

The efficacy of intranasal interferon alpha-2a in respiratory syncytial virus infection in volunteers.

In a double-blind, placebo-controlled study, self-administered intranasal interferon alpha-2a or placebo was given both before and after challenge with respiratory syncytial virus. The incidence of colds and the severity of signs and symptoms were reduced in those receiving interferon alpha-2a as compared with those given placebo. In a further double-blind, placebo-controlled study, self-administered interferon alpha-2a or placebo was given only to those volunteers who developed colds following challenge with respiratory syncytial virus. There was no evidence that interferon alpha-2a reduced the severity of the signs and symptoms or shortened the duration of the illness. The similarity of these results to the effect of interferon alpha-2a in rhinovirus infections in volunteers is discussed.

Administration, Intranasal↗
PubMed1990

Measurement issues in the use of the Coopersmith Self-Esteem Inventory with Navajo women.

In this article the authors describe the measurement error associated with the Coopersmith Self-Esteem Inventory when used with a population of Navajo women. This instrument was used with 29 Navajo women to determine if the questions were culturally acceptable. The results showed that this instrument has some content validity issues when used with Navajo women. More research is needed using this instrument as well as other psychometrically sound self-esteem measures with cultural and racial groups other than whites.

Adolescent↗
PubMed1990

The effect of intranasal nedocromil sodium on viral upper respiratory tract infections in human volunteers.

Two studies involving double-blind group comparative trials in human volunteers compared the effects of intranasal nedocromil sodium (2.6 mg active drug per nostril, q.i.d.) with placebo on clinical symptoms and performance impairment associated with the common cold. In the first study volunteers were challenged with rhinoviruses (RV9 and RV14), and in the second study with respiratory coronavirus. In both studies, active and placebo groups of volunteers were demographically similar. Infection rates in both groups were also similar. There were no withdrawals resulting from unusual symptoms related to either treatment. In the rhinovirus study (19, placebo; 20, nedocromil sodium) daily symptom scores and daily mean nasal secretion weights were significantly lower in the nedocromil sodium-treated group. In the coronavirus study (26, placebo; 27, nedocromil sodium) there was little difference in the severity of colds between the active and placebo-treated groups, but trends favoured nedocromil sodium. In both studies the impairment of performance in volunteers who developed a cold was significantly less in those treated with nedocromil sodium than in those treated with placebo.

Administration, Intranasal↗