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Biomedical subjects

I Phillips

Publications and source records attributed to I Phillips.

At least 19 recordsLinked to original sources
PubMed1998

GABA-evoked depolarisations in the rat cortical wedge: involvement of GABAA receptors and HCO3- ions.

The effect of gamma-aminobutyric acid (GABA) was investigated on cortical wedges prepared from male Sprague-Dawley rats. GABA evoked concentration-dependent depolarisations (EC50: 0.8 mM), which were attenuated by up to 60% when bicarbonate-buffered aCSF was replaced with HEPES-buffered aCSF. Responses to 1 mM GABA were attenuated by (-)-bicuculline and picrotoxin and were potentiated by chlordiazepoxide and pentobarbitone. Ionotropic glutamate receptor antagonists had no effect. We conclude that GABA-evoked depolarisations are mediated via GABAA receptors, arising in part from HCO3- efflux from cells.

Animals↗
PubMed1998

Protective efficacy of a dengue 2 DNA vaccine in mice and the effect of CpG immuno-stimulatory motifs on antibody responses.

A recently described DNA vaccine for dengue (DEN) type 2 was shown to elicit high levels of neutralizing antibodies in mice. The vaccine candidate consists of the PreM and 92% of the envelope genes of DEN 2 New Guinea C strain. We further evaluated this DNA vaccine candidate by examining the effect of immuno-stimulatory CpG DNA motifs on antibody response and by studying the protective efficacy of the vaccine. The results showed that CpG motifs present in pUC 19 significantly improved the antibody response to a suboptimal dose of 3.1 micrograms of the DEN DNA vaccine. In a lethal mouse intracerebral challenge model, the vaccine provided a significant level of protection. Sixty percent of the mice immunized with the DEN DNA vaccine plus pUC 19 survived the challenge compared to only 10% in the control group that received vector plus pUC. These studies illustrate that nucleic acid immunization is a viable approach to developing a DEN vaccine and that immuno-stimulatory CpG DNA motifs can be used to lower the minimum dose required to produce an antibody response.

Adjuvants, Immunologic↗
PubMed1998

Lessons from the past: a personal view.

We know a great deal about the diversity of the genetic and biochemical mechanisms of antibiotic resistance and are thus well equipped by this experience to study new phenomena as they appear in the future. In addition, we have identified relationships between epidemiological patterns in resistance and major external events that we believe are responsible for the development of resistance, namely antibiotic use and the creation of opportunities for the spread of resistance determinants and resistant organisms, although we have tended to ignore these anomalies. However, perhaps because of the latter circumstance, there remain skeptics, both among those who have a particular interest in the subject and, more important, among physicians in general, who are often not persuaded of the relationships between their use of antibacterial drugs and the patterns and prevalence of antibiotic resistance observed by epidemiologists.

Anti-Bacterial Agents↗
PubMed1998

Susceptibility testing of Klebsiella spp.--an international collaborative study in quality assessment.

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure agreement between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment was performed to investigate the performance of susceptibility testing of Klebsiella spp. Ninety-five strains of klebsiellae were selected from clinical isolates at the London Hospital Medical College (LHMC). These included strains with a diversity of susceptibility profiles to amoxycillin/clavulanate, piperacillin, ceftazidime, cefuroxime, ciprofloxacin, gentamicin and trimethoprim. The strains were sent to 13 participating laboratories in Europe and the USA and laboratories were asked to test the susceptibility of these strains to these antibiotics by their usual methods. They were also asked to provide details of the method used to test susceptibility. Several different standard recommended testing methods were used. Reporting of susceptibilities was generally accurate, but a number of anomalies were noted. Discrepancies of reporting between the LHMC and the participating laboratories was more marked for resistant strains, particularly in the detection of resistance to cefuroxime and ciprofloxacin, as well as the assignment of susceptibility and resistance to piperacillin and amoxycillin/clavulanate. Some discrepancies could be attributed to the use of different breakpoints, leading to differing assignment of susceptibility. Methodological variations including disc content, inoculum and failure to measure and interpret zone sizes consistently also led to anomalies. This quality assessment programme has helped to identify problems in susceptibility testing which should be investigated further.

Anti-Bacterial Agents↗
PubMed1998

The 1997 Garrod Lecture. The subtleties of antibiotic resistance.

Although the qualitative aspects of antibiotic resistance are increasingly well understood, our understanding of the quantitative aspects has always lagged. Deficiency of understanding or of investigation affects the methods used to characterize the phenotypes of organisms from clinical sources, delays acquisition of knowledge of the importance of quantitative diversity in patient management, and introduces error into epidemiological studies of the prevalence of resistance. This, in turn, gives rise to a devaluation of the work done in diagnostic laboratories in relation to the technology of sensitivity testing, to the interpretation of their results for clinicians, including those used in clinical trials, and to the statistical analyses of resistance trends used inter alia as a guide to empirical antibiotic therapy and to test the efficacy of methods of control. There is a need to bring about a shift of opinion of those who provide funds, in relation to the role of clinical microbiologists and infectious diseases clinicians in defining and solving these problems.

Anti-Bacterial Agents↗
PubMed1998

Comparative activity of quinupristin/dalfopristin and RPR 106972 and the effect of medium on in-vitro test results.

Quinupristin/dalfopristin and RPR 106972 were active in vitro against a wide range of aerobic Gram-positive organisms including Enterococcus faecium. However, most isolates of Enterococcus faecalis were resistant or of intermediate sensitivity. Against Staphylococcus aureus quinupristin/dalfopristin was more active but for all other species the range of activity of the two drugs was the same or RPR 106972 was more active. RPR 106972 was also more active against the respiratory pathogens Haemophilus influenzae and Moraxella catarrhalis. Quinupristin/dalfopristin MICs for isolates of H. influenzae (1-8 mg/L) clustered around the breakpoint. There were differences in the quality of growth, but little difference in MICs or zone diameters was obtained on three different media: Mueller-Hinton (MHA), Iso-Sensitest (ISA), and Diagnostic Sensitivity Test (DST) agars. The addition of blood to the medium increased MICs 2- to 4-fold, with MHA showing the greatest increase, and reduced zone diameters around quinupristin/dalfopristin discs by 3-4 mm, with the greatest effect on ISA.

Anti-Bacterial Agents↗
PubMed1997

Weak blockade of AMPA receptor-mediated depolarisations in the rat cortical wedge by phenytoin but not lamotrigine or carbamazepine.

The effects of the anticonvulsants, lamotrigine, phenytoin and carbamazepine, were investigated on NMDA and non-NMDA receptor agonist-evoked responses and against spontaneous epileptiform discharges, in the in vitro rat cortical wedge. Lamotrigine weakly attenuated responses to (RS)-alpha-amino-3-hydroxy-5-methoxy-4-isoxazole propionic acid (AMPA) and quisqualate (IC50 values >> 100 microM), but was without effect on responses to NMDA. Phenytoin weakly, but concentration-dependently, attenuated responses to AMPA and quisqualate, but much less potently attenuated responses to NMDA (IC50 values 163, 248 and >> 300 microM, respectively). Carbamazepine (3-100 microM) significantly attenuated responses to NMDA and at 100 microM attenuated responses to AMPA and quisqualate. These effects were not concentration dependent, with the IC50 values >> 100 microM. Lamotrigine and phenytoin weakly, but concentration-dependently, reduced the frequency (IC50 values 254 and > 300 microM, respectively) and amplitude (IC50 values 141 and > 300 microM, respectively) of spontaneous epileptiform discharges, whereas carbamazepine had no effect. The results show that the anticonvulsant effects of these antiepileptics are unlikely to involve antagonism of ionotropic glutamate receptors, although blockade of non-NMDA responses may play a role in the anticonvulsant profile of phenytoin. Furthermore, the data show that clinically effective anticonvulsants do not necessarily attenuate spontaneous epileptiform discharges in the rat cortical wedge.

Animals↗
PubMed1997

An evaluation of near-patient testing for Helicobacter pylori in general practice.

INTRODUCTION: A knowledge of Helicobacter pylori status is likely to be important in the management of patients presenting in general practice with dyspepsia. Near-patient testing kits for the detection of the H. pylori antibodies in whole blood, which provide results very quickly, are now available. AIM: To determine the test characteristics of the Helisal Rapid Blood test in general practice and to describe the ways in which general practitioners incorporate the results of H. pylori testing into their management of patients with dyspepsia. SETTING: Nine general practices in the United Kingdom. PATIENTS: Consecutive patients presenting with dyspepsia in whom further investigation or referral was considered. METHODS: A whole blood fingerstick sample was tested for H. pylori antibodies using the Helisal Rapid Blood test and a venous sample was obtained for subsequent laboratory testing using Helisal Serum and Helico G (ELISA) methods. Results of the three tests were compared and analysed. Clinical data were recorded by the general practitioners. RESULTS: Full serological data were obtained on 123 patients, mean age 44.8 years. The sensitivity and specificity of the Helisal Rapid Blood test, compared with concordant results of the laboratory tests, were 83% and 78%, respectively. The prevalence of H. pylori-positive patients was 57%, with a positive predictive value of 83% and a negative predictive value of 78%. The results of the test had a significant impact on the clinical management of the patients in the study. COMMENT: The Helisal Rapid Blood test is a useful and convenient method of improving the clinical care of patients with dyspepsia in general practice.

Adolescent↗
PubMed1997

Oropouche virus transmission in the Amazon River basin of Peru.

Seroepidemiologic studies were conducted to determine the prevalence of Oropouche (ORO) viral antibody, risk factors, and the incidence of infection among residents of the Amazon region of Peru. Blood samples, as well as demographic, cultural, and medical history data, were collected from residents in a sector of the city of Iquitos and in an adjacent rural and three neotropical rain forest communities. Blood specimens were obtained approximately one year later from a cohort of the same study subjects who were negative for ORO antibody on the initial cross-sectional survey. Sera were tested for ORO IgG antibody by an enzyme-linked immunosorbent assay. Antibody prevalences were 35% for residents of the urban population, 24-46% for the forest communities, and 18% for the rural community. Antibody prevalence increased with age, and subjects who were seropositive were significantly (P = 0.001) older (mean = 33 years) than the seronegative subjects (mean = 15 years). Multivariate analysis revealed that only age, urban and forest residence, and occupation as a farmer or housekeeper remained significantly associated with seropositivity. Seroconversion data for the same populations one year later demonstrated evidence of ORO viral infection among 28% of the residents in the rural community and 2% or less in the forest and urban communities. Oropouche virus infection was significantly associated with older age (P = 0.04) in the rural community (P < 0.001). These data support prior evidence of ORO viral infection among residents of Iquitos and surrounding villages and suggest that transmission of this virus occurs continuously in the population of this area of the Amazon basin.

Adolescent↗
PubMed1997

Standardization of susceptibility testing methods.

Standardization of antibiotic susceptibility tests is desirable but faces several problems. Despite considerable effort, it has been impossible to devise an ideal medium, and discussion continues as to the best inoculum, disk content, atmosphere of incubation, method of reading results, and interpretation of those results in both microbiological and clinical contexts. A range of methods, from manual to almost completely automated, is in current use. Some microbiologists, especially those who use NCCLS methods, advocate the universal adoption of one method for each type of manual test--agar dilution, broth dilution or agar diffusion. Others accept diversity, believing that strict adherence to protocols will make it possible for the results obtained by one method--though not necessarily their interpretation--to be super-imposed on those obtained by other methods.

Microbial Sensitivity Tests↗
PubMed1996

European multicentre evaluation of a commercial system for identification of methicillin-resistant Staphylococcus aureus.

A commercial system for the rapid detection of methicillin-resistant Staphylococcus aureus, the BBL Crystal MRSA test (C-MRSA ID; Becton Dickinson, USA), was evaluated prospectively and compared with a polymerase chain reaction test for the presence of the mecA gene. Ten European centres tested a total of 676 isolates of Staphylococcus aureus from blood cultures. The system correctly identified 661 (97.8%) isolates within 4 h. All but three mecA gene-negative isolates (99.4% specificity) yielded a negative C-MRSA ID reaction, and 158 of 170 mecA gene-positive isolates were accurately detected (92.9% sensitivity). After repeated testing of discrepant results, sensitivity and specificity increased to 99% and 100%, respectively.

Bacteriological Techniques↗
PubMed1996

Cytometric analysis and maturation characteristics of reticulocytes from myelodysplastic patients.

Myelodysplasia is characterized by a hypoproliferative anaemia with ineffective intramedullary erythropoiesis. We have used the novel technology of the Bayer H3 analyser to characterize reticulocytes (RNA containing red cells) from 32 MDS patients and 10 elderly normal subjects. In comparison with reticulocytes from normal subjects, those from MDS patients were larger with a lower haemoglobin concentration. Reticulocytes from sideroblastic patients had a lower haemoglobin content and concentration than for refractory anaemia patients but no other differences between FAB subtypes were found. H3 reticulocyte RNA content parameters correlated poorly with those derived by the Sysmex R-1000, particularly in the MDS group. On reticulocyte maturation to red cells MDS patients concentrated haemoglobin more than normal subjects and this was most evident in the sideroblastic group. Platelet depletion of whole blood suggested that large platelets in the sideroblastic group may have partly contributed to this observation. Prospective evaluation of changes towards normal reticulocyte cytometric parameters may assist in assessment of early erythroid response to therapy in MDS patients.

Adult↗
PubMed1996

Comparative efficacy and safety of single oral doses of sparfloxacin versus ciprofloxacin in the treatment of acute gonococcal urethritis in men.

A double-blind, randomised, international multicentre study was conducted to compare the efficacy and safety of sparfloxacin 200 mg versus ciprofloxacin 250 mg as single oral-dose treatment for acute gonorrhoea in men. A total of 238 patients were included and 191 were evaluable for primary efficacy (eradication of Neisseria gonorrhoeae). At follow-up, 99% (96/97) of the sparfloxacin-treated patients were culture-negative compared with 98% (92/94) in the ciprofloxacin group. Three of the four patients who harboured gonococci at follow-up admitted to having had unprotected sexual intercourse after treatment and were probably reinfections. The rate of post-gonococcal urethritis was 26% in both groups, although Chlamydia trachomatis was isolated in only 4% of patients at inclusion. Both drugs were well tolerated. Single oral doses of sparfloxacin 200 mg and ciprofloxacin 250 mg are equally effective in the treatment of acute gonorrhoea in men.

Acute Disease↗
PubMed1996

A comparative study of two different regimens of sparfloxacin versus doxycycline in the treatment of non-gonococcal urethritis in men.

A multicentre, double-blind, randomised study comparing the efficacy and safety of oral sparfloxacin (200 mg on day 1 followed by 100 mg daily for 2 or 6 additional days) with doxycycline (200 mg once daily for 7 days) in the treatment of non-gonococcal urethritis in men was conducted. The overall success rates for the three treatment groups were statistically equivalent both at the end of treatment and at the follow-up visits. For chlamydial urethritis, the rates of relapse or possible reinfection were similar in the 7-day sparfloxacin and doxycycline groups. For ureaplasmal urethritis and urethritis of unknown aetiology, the rates of relapse or possible reinfection were lower in the 7-day sparfloxacin group than in the other two treatment groups. Sparfloxacin was well tolerated. A 7-day sparfloxacin regimen appears to be a useful alternative to doxycycline for the treatment of non-gonococcal urethritis in men.

Adolescent↗
PubMed1996

Susceptibility testing of Haemophilus influenzae--an international collaborative study in quality assessment.

In order to compare the prevalence of antibiotic resistance in different geographical areas, it is necessary to ensure that agreement is achieved between laboratories on the assignment of strains to 'susceptible' and 'resistant' categories. An international quality assessment study, involving 15 laboratories in eight countries, was performed to investigate the standard of performance of the susceptibility testing of Haemophilus influenzae. One hundred and fifty strains of H. influenzae were distributed from the London Hospital Medical College (LHMC) to all laboratories who were asked to test the susceptibility of the strains to ampicillin, chloramphenicol, tetracycline, trimethoprim, cephalosporins and ciprofloxacin. Laboratories were also asked to provide the details of methodology to test the susceptibility. Significant discrepancy between the LHMC and the participating laboratories appeared in the detection of resistance to ampicillin (especially beta-lactamase-negative strains resistant to ampicillin) as well as the assignment of susceptibility and resistance to chloramphenicol, tetracycline and trimethoprim. Often these reflected the use of inappropriate breakpoints which led to erroneous assignment of susceptibility. Other variations including disc content, medium and supplement, inoculum as well as failure to measure zone sizes properly also led to some repeating anomalies.

Ampicillin↗
PubMed1996

A multinational European survey on the in-vitro activity of rufloxacin and other comparative antibiotics on respiratory and urinary bacterial pathogens.

The antibacterial activity of rufloxacin was confirmed against a large number of respiratory and urinary tract pathogens collected in five European countries. In terms of both MIC90 values and percentages of susceptible isolates found, this new quinolone showed useful in-vitro activity against Mycoplasma catarrhalis, Haemophilus influenzae and Klebsiella pneumoniae, with a large proportion of Staphylococcus aureus also covered, while, as expected Streptococcus pneumoniae and Streptococcus pyogenes were not included in its antibacterial spectrum. Rufloxacin was comparable with the other antibiotics against these pathogens with the exception of streptococci. Against these microorganisms, beta-lactams were the most active agents. Against the urinary pathogens the in-vitro activity of rufloxacin is similar to that of norfloxacin although this latter drug is more active in terms of MIC90 values and in percentages of strains inhibited. In many cases more isolates were susceptible to the remaining comparator agents than to rufloxacin. However, there were no significant differences between the numbers of microorganisms inhibited by the various drugs and rufloxacin. The findings of this survey do not seem to modify the general picture which emerged in previous studies and further confirms its useful spectrum in different geographic settings.

Anti-Bacterial Agents↗
PubMed1996

The epidemiology of HIV-1 infection in Peru, 1986-1990.

OBJECTIVE: To determine the extent of the HIV-1 epidemic in Peru. DESIGN: Part of a national serosurvey in Peru. METHODS: Between January 1986 and December 1990, 140,976 serum samples were tested for HIV-1 antibody. RESULTS: HIV-1 antibody was found in a high percentage of serum samples provided by 4300 homosexual men (26%), 2204 male sexually transmitted disease patients (10%), 145 drug users (13%), 269 hemophiliacs (10%), and 146 unlicensed female prostitutes (10%). In addition, the prevalence of HIV-1 infection increased substantially among these groups between the beginning and end of the survey period. A low but rising prevalence of HIV-1 antibody was found during this period among serum samples provided by 83,526 blood donors and 11,101 military personnel:total period prevalence, 0.25 and 0.32%, respectively. CONCLUSION: These data indicate that HIV-1 infection is epidemic in Peru among groups at high risk of sexually and parenterally transmitted diseases, and that the risk of infection appears to be low but possibly increasing among the general population.

Disease Outbreaks↗