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Biomedical subjects

I Phillips

Publications and source records attributed to I Phillips.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Pulmonary aspiration complicating intraoperative small-bowel decompression: a case report and literature review.

When conservative management of intestinal obstruction fails, the surgeon has two operative choices for decompression: the open procedure with enterotomies and suction and the closed procedure consisting of retrograde stripping and nasogastric suction. A previously undocumented complication of the latter procedure-pulmonary aspiration-is reported in a 20-year-old man with small-bowel obstruction. Practical modifications to the technique of small-bowel decompression are suggested. They include feeding the nasogastric tube into the distal duodenum, using a wider bore tube, inserting an esophageal balloon before extubation, using a nasogastric tube with suction throughout extubation and, immediately postoperatively, making a more conscious effort to remove all gastric contents before extubation, and milking the contents distally through the ileocecal valve.

Adult↗
PubMed1995

Dopamine D2 receptors: a potential pharmacological target for nomifensine and tranylcypromine but not other antidepressant treatments.

Treatment for 1 or 14 days by IP injection with the antidepressants, amitriptyline (10 mg/kg), bupropion (30 mg/kg), desipramine (10 mg/kg), GBR 12909 (10 mg/kg), sibutramine HCl (3 mg/kg), mianserin (5 mg/kg), and zimeldine (10 mg/kg), did not affect the number or affinity of dopamine D2 receptors determined by [3H]raclopride binding to rat striatal membranes. Similarly, neither did a single, nor repeated (five times over 10 days), electroconvulsive shock, given under halothane anaesthesia, have any effect on [3H]raclopride binding parameters. By contrast, the noradrenaline and dopamine reuptake inhibitor, nomifensine (5 mg/kg), and the monoamine oxidase inhibitor, tranylcypromine (5 mg/kg), decreased the number of dopamine D2 receptors by 12% and 11%, respectively, when given for 14 days. Administration of the D2 receptor antagonist, haloperidol (1 mg/kg), for 14 days increased the number of [3H]raclopride binding sites by 17%. Thus, the data demonstrate that although nomifensine and tranylcypromine decrease D2 receptor number after 14 days administration, this adaptive change is not observed with other antidepressant treatments. However, the findings do not preclude a contribution of altered dopamine D2 receptor function to the efficacy of those drugs with potent effects on dopaminergic neuronal function.

Animals↗
PubMed1995

The ability of beta-lactam antibiotics to select mutants with derepressed beta-lactamase synthesis from Citrobacter freundii.

The ability of beta-lactam compounds to induce synthesis of the class C beta-lactamase of Citrobacter freundii was assessed both directly and indirectly, the latter by measurement of the different susceptibilities of strains with inducible and depressed beta-lactamase synthesis and those of a beta-lactamase-negative strain. Most beta-lactam compounds were poor inducers but ampicillin, amoxycillin and cephalexin were moderately good inducers and cefoxitin, imipenem and meropenem were strong inducers. The ability of the compounds to select mutants in which the synthesis of the beta-lactamase was derepressed was also assessed. Imipenem and temocillin, which had a high degree of stability to the beta-lactamase failed to select such mutants or were very poor selectors. In contrast, most other compounds showed considerable lability to the beta-lactamase and readily selected derepressed mutants, whether they were strong inducers of beta-lactamase synthesis (for example cefoxitin) or poor inducers (cefotaxime, ceftazidime and many other compounds). Thus it appears that lability to the beta-lactamase is a more important factor in determining whether or not a compound will select derepressed mutants than the power of the compound as an inducer of beta-lactamase synthesis, since induction results in the production of less beta-lactamase than derepression as a result of mutation.

Anti-Bacterial Agents↗
PubMed1995

Resistance to imipenem in Pseudomonas aeruginosa.

There was a slow increase in imipenem resistance in Pseudomonas aeruginosa at St. Thomas' Hospital in the 1990s, reaching 3% in 1994. Of the 94 imipenem-resistant strains, 69% were susceptible to all the other agents tested; 15% were also resistant to one other antibiotic, 5.3% to two, 6.4% to three, 4.3% to four or more compounds. 16% of strains were resistant to at least one other beta-lactam in addition to imipenem. Resistance to other antibiotics was more common among the strains for which imipenem MICs were 4 mg/L than among either imipenem-susceptible or imipenem-resistant (MICs > or = 8 mg/L) strains.

Anti-Bacterial Agents↗
PubMed1995

In-vitro activity of purpuromycin and MDL 63,604 against microorganisms that cause vaginitis and vaginosis.

Purpuromycin and its semi-synthetic derivative MDL 63,604 had in-vitro activity similar to that of amphotericin B against isolates of Candida albicans. MDL 63,604 had activity similar to that of metronidazole against Trichomonas vaginalis. Both compounds were very active against most species of Gram-positive and Gram-negative anaerobes and against Gardnerella vaginalis. MDL 63,604 had significantly lower MICs than purpuromycin against T. vaginalis and most of the bacteria, probably due to antagonism of purpuromycin's activity by medium supplements (blood or serum). Purpuromycin or related compounds may have a potential role in the topical treatment of vaginitis and vaginosis.

Amphotericin B↗
PubMed1995

Mechanisms of hyperproduction of TEM-1 beta-lactamase by clinical isolates of Escherichia coli.

The mechanisms of hyperproduction (defined as > or = 200 nmoles nitrocefin hydrolysed per minute per mg of protein) of TEM-1 beta-lactamase by 38 isolates of Escherichia coli were investigated. The copy numbers of TEM-encoding plasmids were determined for the hyperproducing isolates and for 39 TEM-1-producing isolates that did not hyperproduce the enzyme. Allele-specific PCR was used to determine if the promoter region of the TEM-1 gene was of the TEM-1 or TEM-2 type. Twenty three of the 38 hyperproducers had the TEM-1-type promoter but 15 had the more efficient TEM-2-type promoter; in contrast, 37 of the 39 isolates with lower activities had the TEM-1-type promoter and only two had the TEM-2-type promoter. Many of the TEM-1-hyperproducing isolates possessed small plasmids (< or = 20 MDal) with high copy numbers, in some cases together with large, low copy number plasmids; the average total copy number of TEM-encoding plasmids was 14; if only isolates with the TEM-1-type promoter were included, average total copy number was 22. Hyperproduction was attributed to high copy number (> or = 10) plasmids in 11 isolates; another seven had plasmids with moderately high copy numbers (4-9). The average total copy number for isolates that produced relatively small amounts of TEM-1 beta-lactamase (< or = 100 nmoles/min/mg protein) was 2.2, and for the 12 isolates with TEM-1 activities of 101-200 nmoles/min/mg protein it was 6.8. We conclude that both high copy number plasmids and a more efficient promoter are common causes of hyperproduction of TEM-1.

Alleles↗
PubMed1995

Adherence characteristics of coagulase-negative staphylococci isolated from patients with infective endocarditis.

Coagulase-negative staphylococci isolated from patients with endocarditis were divided according to whether the infection was of native or of prosthetic valves and was acquired either in the community or in hospital. Comparisons were made with strains from intravenous line-associated bacteraemias. All strains were examined by direct and indirect adherence tests. Line-associated bacteraemia strains were more likely to produce slime and were more hydrophilic but were less likely to attach HEp2 tissue culture cells than were endocarditis strains, and almost equally likely to adhere to plastic and extracellular matrix proteins. Amongst the endocarditis strains, there was little difference in slime production but hospital-acquired or prosthetic-valve strains were more hydrophobic and more likely to adhere to silicone than were the native-valve or community-acquired strains. Exposure of extracellular matrix proteins on native valves due to a pre-existing non-infective heart condition may account for the selection of strains able to adhere to fibronectin or laminin.

Bacteremia↗
PubMed1995

The effect of topical fluticasone propionate on intranasal histamine challenge in subjects with perennial allergic rhinitis.

The mechanism of action of topical intranasal steroids is obscure. To investigate this, we have studied the effects of a topical intranasal corticosteroid, fluticasone propionate on nasal airflow resistance (Rnaw), secretions, cytological smears and symptoms. Fluticasone propionate aqueous nasal spray was given to 11 patients with perennial allergic rhinitis in a double-blind, placebo-controlled study. On each day, patients were challenged with ascending doses of histamine. Rnaw, secretion volume, total protein, mucin, lysozyme and albumin were measured. Nasal smears were taken and sneezes counted. Diary card data were collected for both treatment periods. There was a significant, dose-related increase in Rnaw and sneezing on histamine challenge. A single dose of fluticasone had no effect on any parameter. After 4 weeks of treatment, resistance measurements were reduced (post-challenge g.m.2.8 cmH2O/l/s, Q1-Q3 1.6-4.8; placebo 4.2, 2.9-5.3: P < 0.0001) as were baseline secretion volumes (mean 2.4 ml/5 min, c.i.1.9-3.0; placebo 3.3, 2.8-3.8: P < 0.05). Eosinophil counts were suppressed (fluticasone 5.8%, c.i. 4.0-15.7; placebo 23.3%, 12.4-34.1: P < 0.05) and the composite symptom score reduced (P < 0.05). Fluticasone has long-term effects on the nasal response to histamine in perennial allergic rhinitis and part of this effect is likely to be vascular.

Administration, Topical↗
PubMed1995

Incidence and mechanisms of resistance to the combination of amoxicillin and clavulanic acid in Escherichia coli.

Among Escherichia coli organisms isolated at St. Thomas's Hospital during the years 1990 to 1994, the frequency of resistance to amoxicillin-clavulanic acid (tested by disk diffusion in a ratio of 2:1) remained constant at about 5% of patient isolates (10 to 15% of the 41 to 45% that were amoxicillin resistant). Mechanisms of increased resistance were determined for 72 consecutively collected such amoxicillin-clavulanic acid-resistant isolates. MICs of the combination were 16-8 micrograms/ml for 51 (71%) of these and > or = 32-16 micrograms/ml for the remainder. The predominant mechanism was hyperproduction of enzymes isoelectrically cofocusing with TEM-1 (beta-lactamase activities, > 200 nmol of nitrocefin hydrolyzed per min per mg of protein) which was found in 44 isolates (61%); two isolates produced smaller amounts (approximately 150 nmol/min/mg) of such enzymes, and two isolates hyperproduced enzymes cofocusing with TEM-2. Eleven isolates produced enzymes cofocusing with OXA-1 beta-lactamase, which has previously been associated with resistance to amoxicillin-clavulanic acid. Ten isolates produced increased amounts of chromosomal beta-lactamase, and four of these additionally produced TEM-1 or TEM-2. Three isolates produced inhibitor-resistant TEM-group enzymes. In one of the enzymes (pI, 5.4), the amino acid sequence change was Met-67-->Val, and thus the enzyme is identical to TEM-34. Another (pI, 5.4) had the substitution Met-67-->Ile and is identical to IRT-I67, which we propose now be given the designation TEM-40. The third (pI, 5.2) had the substitution Arg-241-->Thr; this enzyme has not been reported previously and should be called TEM-41. The rarity and diversity of inhibitor-resistant TEM-group enzymes suggest that they are the result of spontaneous mutations that have not yet spread.

Amoxicillin↗
PubMed1995

DNA sequence differences of ampD mutants of Citrobacter freundii.

Three groups of mutants with increased levels of beta-lactamase synthesis were selected from Citrobacter freundii 382010 by beta-lactam antibiotics at concentrations just above the MIC. Uninduced cultures of the hyperinducible group had 3- to 5-fold more beta-lactamase activity than the parent strain, with one mutant (termed type b) expressing 19 times the activity of the parent strain; the partially derepressed group had a relative 55-fold increase, while fully derepressed strains exhibited a 460-fold increase. Upon induction by growth in the presence of cefoxitin (32 micrograms/ml) for 2 h, the hyperinducible and derepressed groups had similar relative beta-lactamase activities of 650 and 725, respectively. Induction of beta-lactamase activity from partially derepressed mutants resulted in a relative activity of only 240. The ampD gene including its promoter region was amplified from the parent strain and the mutant strains by PCR. The sequence of ampD from the parent strain showed only three nucleotide changes from a previously published sequence, none of which resulted in a change to the deduced amino acid sequence. Hyperinducible mutant strains of type a had an amino acid change of either a tryptophan in codon 95 to an arginine (Trp-95-->Arg) (three mutants) or Ala-158-->Asp (one mutant). The hyperinducible type b strain had the change Tyr-102-->Asp. The derepressed strains had the following changes: Val-33-->Gly (one mutant), Asp-164-->Glu (one mutant), and Trp-95-->termination codon (two mutants). We infer that the amino acid changes in the hyperinducible mutants result in altered AmpD activity, whereas, in contrast, they lead to an inactive protein in derepressed mutants. No nucleotide differences were found in the ampD gene from partially derepressed strains.

Anti-Bacterial Agents↗
PubMed1995

Antibacterial action of ciprofloxacin.

The mechanisms by which quinolones rapidly kill are ill defined. We have investigated the action of ciprofloxacin on Escherichia coli KL16 with a combination of traditional and flow cytometric methods and have analyzed cells for changes in membrane potential, membrane integrity, oxidative metabolism, morphology, and viability. Log-phase cultures were exposed to various concentrations (0.1, 1, 10, and 100 times the MIC) of ciprofloxacin and analyzed at regular intervals over 120 min. We also measured protein synthesis in the related strain PQ37 cultured under the same conditions over 300 min, using a colorimetric assay for beta-galactosidase release. Despite a 3-log order decrease in CFU after 60-min exposure to 10 and 100 times the MIC of ciprofloxacin, there was no equivalent decrease in bacterial numbers as determined by both light microscopy and flow cytometry. Furthermore, while these bacteria showed concentration-dependent morphological changes, most were capable not only of excluding the fluorescent nucleic acid-binding dye propidium iodide, but also of reducing the tetrazolium dye cyanoditodyl tetrazolium chloride. Over 90% of the bacteria maintained a membrane potential [as determined by exclusion of bis-[1,3-dibutylbarbituric acid) trimethine oxonol] when exposed to ciprofloxacin for 120 min, except at 100 times the MIC, when this figure fell to < 10%. Finally, protein synthesis was either maintained or induced at all concentrations of ciprofloxacin up to 5 h postexposure. Taken together, these results demonstrate the continuing physical and metabolic survival of ciprofloxacin-exposed bacteria; we suggest parallels with the concept of the viable nonculturable state.

Anti-Infective Agents↗