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Biomedical subjects

I Phillips

Publications and source records attributed to I Phillips.

At least 91 records · Page 5Linked to original sources
PubMed1992

Effects of valproate on xenobiotic biotransformation in rat liver. In vivo and in vitro experiments.

Male Wistar rats were in vivo exposed for 2 weeks to 100 micrograms/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As an in vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200 micrograms/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarin O-deethylase, aldrin epoxidase and glutathione S-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P-450 content and the 7-ethoxycoumarin O-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathione S-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronounced in vitro than in vivo.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1992

Antibiotic sensitivity of the Bacteroides fragilis group in Europe. European Study Group.

Rates of resistance to 12 antibiotics were determined for 1,289 isolates of Bacteroides fragilis group submitted in 1988-1989 by 22 laboratories in 15 European countries. There was no resistance to metronidazole (breakpoint 8 mg/l) and only one isolate was resistant to chloramphenicol (breakpoint 8 mg/l). Resistance was uncommon for imipenem (0.3% at greater than 4 mg/l), amoxicillin/clavulanate (1% at greater than 8 mg/l), cefoxitin (3% at greater than 32 mg/l), mezlocillin (6% at greater than 64 mg/l) and clindamycin (9% at greater than 4 mg/l). Resistance was the rule for ampicillin (93% at greater than 4 mg/l), ciprofloxacin (56% at greater than 4 mg/l) and tetracycline (64% at greater than 4 mg/l). Bacteroides fragilis, the commonest species, was generally the most sensitive: resistance of this organism was uncommon for cefotetan (4% at greater than 32 mg/l) and ceftazidime (12% at greater than 32 mg/l) to which the other species were more often resistant. There were small but significant differences between laboratories and countries for many of the antibiotics. Regionally the most striking differences were for clindamycin where resistance in Bacteroides fragilis was most common in the South and for tetracycline where resistance in Bacteroides fragilis, Bacteroides thetaiotaomicron and Bacteroides uniformis was least common in the North.

Anti-Bacterial Agents↗
PubMed1992

Controlled trial of a Y-set dialysis delivery system to prevent peritonitis in patients receiving continuous ambulatory peritoneal dialysis.

Peritonitis rates were compared in patients receiving continuous ambulatory peritoneal dialysis (CAPD) via either a Y-set dialysate delivery system or a standard system. Forty patients in each arm of the trial were matched for age (range 20-67 years, mean 49 years), and remained in the study for similar periods (range 3-36 months, mean 14.1 months). The observation time was 564 patient-months for each arm of the trial. There were 22 episodes of peritonitis in nine out of 40 patients using the Y-set and 57 episodes in 21 out of 40 patients using the standard system (P = 0.005 Wilcoxon signed rank test for episodes, P = 0.02 McNemar's chi 2 test for patients). Peritonitis rates were one episode per 25 patient-months in the Y-set group, and one episode per 9.7 patient-months in the standard group. In the Y-set group there were significantly fewer episodes caused by coagulase-negative staphylococci and Acinetobacter spp. There was no difference in the rate of episodes caused by Staphylococcus aureus, streptococci, enterococci, corynebacteria, enterobacteria or pseudomonads. There was no difference in the incidence of catheter exit wound infections. The Y-set dialysis delivery system is effective in reducing peritonitis rates in CAPD patients caused by organisms derived from the commensal skin flora, principally coagulase-negative staphylococci, but does not reduce peritonitis caused by other organisms.

Acinetobacter↗
PubMed1992

Detection of ciprofloxacin resistance in gram-negative bacteria due to alterations in gyrA.

Two plasmids containing the cloned Escherichia coli wild-type gyrA gene were used to transform ciprofloxacin-resistant Gram-negative clinical isolates to screen for DNA gyrase A-mediated quinolone resistance. The results show that the technique is simple and applicable to a wide range of Gram-negative species including E. coli, Enterobacter cloacae, Klebsiella aerogenes, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Campylobacter jejuni and Neisseria gonorrhoeae. The use of an arithmetical MIC series of dilutions (as opposed to standard geometrical ones) was found to be essential during screening for the detection of altered gyrase A. The observations were consistent with the suggestion that DNA gyrase is highly conserved among different species of bacteria and that gyrase A-mediated resistance can occur in all.

Ciprofloxacin↗
PubMed1992

Prevalence of resistance to beta-lactam antibiotics in Escherichia coli isolated from blood from 1969-1991.

MICs of beta-lactam antibiotics were determined for blood culture isolates of Escherichia coli from patients in St. Thomas' Hospital, London between 1969 and 1991. There was correlation between MICs of carbenicillin and those of amoxycillin (Kendall's coefficient of rank correlation, tau = 0.67), mezlocillin (tau = 0.73), cephaloridine (tau = 0.64) and amoxycillin/clavulanic acid (tau = 0.72), but less correlation between MICs of carbenicillin and cefuroxime (tau = 0.31). During the two decades, the geometric mean MICs increased for carbenicillin (6.6-fold increase in mean MIC), mezlocillin (3.4-fold increase in mean MIC), cephaloridine (two-fold increase in mean MIC) and, to a smaller extent, amoxycillin/clavulanic acid (1.2-fold increase in mean MIC), but not for cefuroxime. These changes were the result of increases in the proportion of isolates that were resistant to carbenicillin and not of changes in the phenotype of carbenicillin-resistant isolates.

Amoxicillin↗
PubMed1992

Induction of the SOS gene (umuC) by 4-quinolone antibacterial drugs.

Induction by the 4-quinolone group of antibacterial drugs of the umuC gene, the SOS function most involved in error-prone DNA repair (together with umuD), was assessed in a strain of Escherichia coli harbouring a umuC::lacZ gene fusion. All 4-quinolones tested induced this umuC::lacZ fusion, with maximum induction at 4-quinolone concentrations close to their minimum inhibitory concentrations for this strain, and the SOS Inducing Potential (SOSIP) was closely related to antibacterial activity. Mitomycin C, a known mutagen, was a slightly better inducer (in terms of SOSIP) than any of the quinolones. In contrast, induction by 4-quinolones of the sfiA (sulA) gene, an SOS function involved in cell division inhibition, was better than induction by mitomycin C in an E. coli strain harbouring an sfiA::lacZ gene fusion. The umuC gene fusion was induced at lower concentrations of 4-quinolone than was the sfiA gene fusion.

4-Quinolones↗
PubMed1992

Evaluation of methods for typing coagulase-negative staphylococci.

One hundred and forty-two coagulase-negative staphylococci (CNS) isolated from dialysate effluent or skin of patients receiving continuous ambulatory peritoneal dialysis (CAPD) were typed by extended antibiogram (16 antibiotics) and biotype (26 reactions). These isolates were then typed by supplementary methods to determine the most suitable typing method for an epidemiological study of antibiotic resistance. These included phage typing, reverse phage typing, plasmid typing, whole-cell protein typing by SDS-PAGE with analysis by densitometry, and immunoblotting. The percentage of isolates typed successfully by the supplementary methods were: phage typing 20%, reverse phage typing 0%, plasmid typing 66%, SDS-PAGE 100%, immunoblotting 100%. The discrimination of each method was: phage typing 20%, plasmid typing 37%, SDS-PAGE 69%, immunoblotting 57%. Reproducibility was 88% for phage typing and 97% for plasmid typing. The reproducibility of the whole-cell protein typing was 83% if the same extracts were used but only 43% when separate protein extracts were analysed on separate occasions. However, strain relatedness was highly reproducible. The determination of an antibiogram-biotype profile was not a sufficiently accurate typing method for an epidemiological study of antibiotic resistance. Whole-cell protein typing by SDS-PAGE or immunoblotting was technically demanding but was the most effective of the supplementary methods for detecting erroneous discrimination and false matching produced by antibiogram-biotype combinations.

Bacterial Proteins↗
PubMed1992

Opposing roles for 5-HT1B and 5-HT3 receptors in the control of 5-HT release in rat hippocampus in vivo.

1. Intracerebral microdialysis was used to determine whether 5-hydroxytryptamine (5-HT) release in the ventral hippocampus of rats anaesthetized with chloral hydrate was modulated by 5-HT3 receptors. 2. It was confirmed that 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969), a selective 5-HT1B receptor agonist, decreased 5-HT release in a dose- and concentration-related manner when administered i.p. (1 and 5 mg kg-1) or via the dialysis probe (0.1 and 1 microM) respectively. The effect of RU 24969 infusion (1 microM) was attenuated by concurrent infusion of metitepine (10 microM) into the hippocampus. 3. When infused into the hippocampus for 15 min, the selective 5-HT3 receptor agonist, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT; 0.1- 10 microM) increased dialysate 5-HT levels in a concentration-related manner; an effect which was abolished by concurrent infusion of 3-tropanyl-3,5-dichlorobenzoate (1 microM, MDL 72222), a selective 5-HT3 antagonist. 4. MDL 72222 had no effects on hippocampal 5-HT release when administered via the dialysis probe (1 or 10 microM). 5. The data show that 5-HT3 and 5-HT1B receptors have opposing roles in the control of 5-HT release in the hippocampus, with 5-HT3 receptors facilitating and 5-HT1B receptors inhibiting 5-HT efflux, respectively. They also indicate that the facilitatory 5-HT3 receptors are not tonically activated.

Animals↗
PubMed1992

Characterization of 8-OH-DPAT-induced hypothermia in mice as a 5-HT1A autoreceptor response and its evaluation as a model to selectively identify antidepressants.

1. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose-dependently induced hypothermia in mice. 2. The 5-HT1A receptor partial agonists, buspirone, gepirone and ipsapirone, also dose-dependently induced hypothermia. 3. The 8-OH-DPAT temperature response was antagonized by the 5-HT1 receptor antagonists quipazine (2 mg kg-1, i.p.), (+/-)-propranolol (10 mg kg-1, i.p.). (+/-)-pindolol (5 mg kg-1, i.p.), spiroxatrine (0.5 mg kg-1, i.p.) and metitepine (0.05 mg kg-1, i.p.), but not by 5-HT2 (ketanserin) or 5-HT3 (MDL 72222, GR 38032F) receptor antagonists. 4. The response was also antagonized by the dopamine D2 receptor antagonists, haloperidol and BRL 34778. No other catecholamine or muscarinic receptors were involved in mediating the response. 5. Destruction of 5-hydroxytryptamine (5-HT)-containing neurones with the neurotoxin, 5,7-dihydroxytryptamine (75 micrograms, i.c.v.), abolished the response to 8-OH-DPAT indicating that the 5-HT1A receptors involved were located on 5-HT neurones. 6. Chronic antidepressant treatment down-regulated this 8-OH-DPAT response. In addition, chronic administration of anxiolytics and neuroleptics was also effective in this respect. Down-regulation was also observed following repeated administration of 8-OH-DPAT (0.5 mg kg-1, s.c.), (+/-)-pindolol (10 mg kg-1, i.p.) and ketanserin (0.5 mg kg-1, i.p.). 7. In conclusion, these data confirm that 8-OH-DPAT-induced hypothermia is mediated by 5-HT1A autoreceptors. They also indicate that the response involves D2 receptors.The present study also shows that a wide range of antidepressant drugs down-regulate this response although this property is not restricted to antidepressant treatments. Therefore, care should be exercised when interpreting data from this paradigm.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

First documented outbreak of dengue in the Peruvian Amazon region.

This article describes a classical dengue outbreak caused by dengue serotypes 1 and 4 that occurred from March to July 1990 in the city of Iquitos and surrounding areas of Loreto Department in the Peruvian Amazon. Epidemiologic data indicate that more than 150,000 persons may have been affected in Iquitos alone. Another dengue outbreak occurred in Tarapoto, a city in the neighboring department of San Martín. Laboratory data indicate that the same dengue serotypes were involved in both outbreaks. No cases of dengue hemorrhagic fever/shock syndrome appear to have occurred. Prior to this outbreak, no indigenous dengue cases had been documented in Peru.

Dengue↗
PubMed1992

The epidemiology of ciprofloxacin resistance in coagulase-negative staphylococci in CAPD patients.

Ciprofloxacin was used as empirical therapy for peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD) for 26 months, providing an opportunity to study the epidemiology of ciprofloxacin resistance amongst coagulase-negative staphylococci (CNS). Swabs were collected from the CAPD patients, staff, and clinic environment before, during and after the time this antibiotic was prescribed. Clinical isolates were also studied, and records kept of patient hospital attendance. Ciprofloxacin-resistant staphylococci were typed by antibiogram, biotype, plasmid profile, SDS-PAGE, and immunoblotting. No resistant strains were detected before the use of ciprofloxacin. During its use 30% of patients became skin carriers, and resistant strains caused 8% of peritonitis episodes in 7% of patients (38% of carriers). Resistant strains were isolated from the environment, but never from attending members of staff. A total of 208 resistant isolates with MIC's between 8 and 128 mg/l was collected and identified as Staphylococcus epidermidis or S. haemolyticus. Sixteen strain types were distinguished. There was epidemiological evidence for selection of resistant strains derived from the host commensal flora and also for cross-colonization, and cross-infection. Carriage of resistant strains fell to 15% of patients, 6 months after the use of ciprofloxacin had ceased.

Air Microbiology↗
PubMed1991

In vitro activity of cefpodoxime, a new oral cephalosporin, compared with that of nine other antimicrobial agents.

The in vitro activity of the compound RU-51746, the sodium salt of cefpodoxime (which is administered orally as the ester cefpodoxime proxetil) was compared with that of other commonly used oral antibiotics against a selection of clinical isolates of common bacteria from patients with urinary tract, soft tissue and respiratory tract infections. RU-51746 was found to inhibit 90% of Enterobacteriaceae at less than 1 mg/l; pneumococci, pyogenic streptococci (Lancefield groups A, C and G) and Streptococcus agalactiae were almost all inhibited by concentrations of less than 0.06 mg/l; Haemophilus influenzae (including beta-lactamase producers) were inhibited by less than 1 mg/l; 90% of Branhamella catarrhalis were inhibited at less than 2 mg/l. Activity against Acinetobacter spp. and staphylococci was variable and enterococci were all resistant.

Acinetobacter↗