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Biomedical subjects

M V Martin

Publications and source records attributed to M V Martin.

At least 55 records · Page 3Linked to original sources
PubMed1999

The use of fluconazole and itraconazole in the treatment of Candida albicans infections: a review.

Candida albicans is responsible for most fungal infections in humans. Fluconazole is well established as a first-line management option for the treatment and prophylaxis of localized and systemic C. albicans infections. Fluconazole exhibits predictable pharmacokinetics and is effective, well tolerated and suitable for use in most patients with C. albicans infections, including children, the elderly and those with impaired immunity. Prophylactic administration of fluconazole can help to prevent fungal infections in patients receiving cytotoxic cancer therapy. The increasing use of fluconazole for the long-term prophylaxis and treatment of recurrent oral candidosis in AIDS patients has led to the emergence of C. albicans infections that are not responsive to conventional doses. Second-line therapy with a wider spectrum antifungal, such as itraconazole, should be sought if treatment with fluconazole fails. A solution formulation of itraconazole has recently been introduced to overcome the poor and variable absorption of its original capsule formulation. Efficacy and tolerability studies in HIV-positive or immunocompromised patients with C. albicans infections have shown that, although itraconazole solution is as effective as fluconazole, it is less well tolerated as first-line therapy. Itraconazole solution can be effective in AIDS patients with C. albicans infections that are non-responsive to fluconazole. No efficacy or tolerability data are available on the use of itraconazole solution in children or the elderly.

Antifungal Agents↗
PubMed1999

Orthodontics and infective endocarditis.

Infective endocarditis associated with orthodontics is a rare occurrence. Unfortunately, many orthodontic practitioners do not treat patients potentially at risk of developing endocarditis due to the lack of practical guidelines and fear of precipitating the infection. Additionally, many patients that undergo orthodontic treatment are inappropriately prescribed antibiotic cover for procedures that have a minimal bacteraemic risk. In this paper the literature linking orthodontic treatment and infective endocarditis is examined. Recommendations are made for the appropriate management of patients at risk of infective endocarditis for orthodontic procedures. Refereed Paper

Adult↗
PubMed1998

An investigation of the effect of repeated autoclaving on the speed of some dental turbines in general dental practice.

OBJECTIVE: To determine if five types of turbine handpieces could withstand autoclaving in dental practice. METHOD: Five makes of handpieces were used sequentially by four NHS dental practices in the UK. The practitioners oiled and autoclaved the handpieces after every patient use according to the manufacturer's instructions. The number of times the turbine was used and for what procedure was noted. The turbine use was discontinued when the practitioner perceived a significant fall in handpiece performance and the output speed measured. RESULTS: Only one handpiece withstood one year of use in practice with a 1.8% drop in output speed. The other four handpieces had drops in output speeds of 23.5-63.6%. CONCLUSIONS: The results of this survey confirm that some handpieces do not withstand autoclaving. It is also suggested that the tests used in this investigation represent a good assessment of whether a handpiece can withstand autoclaving. It would be useful if data comparable to that described in this paper were available for all handpieces.

Dental High-Speed Equipment↗
PubMed1998

Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cytochrome P450 1A2.

The dietary mutagens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are activated to genotoxins by rat and human liver cytochrome P450 (P450) 1A1- and 1A2-mediated N-oxidation. Immunoquantitation of 51 human liver samples revealed a wide range in P450 1A2 expression (10-250 pmol/mg of microsomal protein, median 71 pmol/mg), with 39% of the livers containing >100 pmol/mg of protein. There was no evidence for expression of P450 1A1 (<1 pmol/mg of protein). P450 1A2 levels were correlated to MeIQx and PhIP N-oxidation rates (r = 0.83, 0.73, respectively). In male Fischer-344 and Sprague-Dawley rats, hepatic P450 1A2 ranged from 5 to 35 pmol/mg of protein, while P450 1A1 was <1 pmol/mg. Animal pretreatment with 3-methylcholanthrene, beta-naphthoflavone, or polychlorinated biphenyls (PCB) resulted inasmuch as 340-fold and >1000-fold induction of P450 1A2 and 1A1, respectively, and a 220-fold increase in N-oxidation activity. Approximately 20% of the human samples were as active in N-oxidation and conversion of MeIQx to bacterial mutagens as microsomes of PCB-pretreated rats [3-4 nmol of NHOH-MeIQx formed min-1 (mg of protein)-1]. In contrast, microsomes from PCB-treated rats displayed higher rates of PhIP N-oxidation and activation to mutagens than the most active human liver microsomes [8-24 vs 2-4 nmol of HNOH-PhIP formed min-1 (mg of protein)-1]. Recombinant human P450 1A2 showed catalytic efficiencies of MeIQx and PhIP N-oxidation that were 10-19-fold higher than purified rat P450 1A2. Cytochrome P450 1A2 expression in rodent and human liver tissue varies greatly and there are considerable differences between the enzymes in the two species in the activation of some heterocyclic aromatic amines, which must be considered when assessing human health risk.

Animals↗
PubMed1997

Detection of free radicals produced from the reaction of cytochrome P-450 with linoleic acid hydroperoxide.

The ESR spin-trapping technique was employed to investigate the reaction of rabbit cytochrome P-450 1A2 (P450) with linoleic acid hydroperoxide. This system was compared with chemical systems where FeSO4 or FeCl3 was used in place of P450. The spin trap 5, 5'-dimethyl-1-pyrroline N-oxide (DMPO) was employed to detect and identify radical species. The DMPO adducts of hydroxyl, O2-., peroxyl, methyl and acyl radicals were detected in the P450 system. The reaction did not require NADPH-cytochrome P-450 reductase or NADPH. The same DMPO-radical adducts were detected in the FeSO4 system. Only DMPO-.OH radical adduct and carbon-centred radical adducts were detected in the FeCl3 system. Peroxyl radical production was completely O2-dependent. We propose that polyunsaturated fatty acids are initially reduced to form alkoxyl radicals, which then undergo intramolecular rearrangement to form epoxyalkyl radicals. Each epoxyalkyl radical reacts with O2, forming a peroxyl radical. Subsequent unimolecular decomposition of this peroxyl radical eliminates O2-. radical.

Animals↗
PubMed1997

Acute dentoalveolar infections: an investigation of the duration of antibiotic therapy.

OBJECTIVE: To evaluate shortened courses of antibiotics in the management of dentoalveolar abscesses. DESIGN: Prospective clinical study over a 3-year period. SETTING: Examinations department of the Liverpool University Dental Hospital. SUBJECTS: 759 patients, with acute dentoalveolar abscesses associated with swelling, and an elevation of axillary temperature to above 38.5 degrees C, were included in the investigation. The minimum age of the patients was 16 years. INTERVENTIONS: The initial treatment was to drain the abscess by incision (124 patients), or extraction (635). The patients were prescribed amoxycillin (250 mg every 8 hours), clindamycin (150 mg every 6 hours) or erythromycin stearate (250 mg every 6 hours) and instructed to drink plenty of fluid. All the patients were seen 2 or 3 and 10 days later; only patients who were seen at these times were included in the trial. MAIN OUTCOME MEASURES: Resolution of the swelling and a normal axillary temperature. RESULTS: At first review 748 patients (98.6%) had normal temperatures, marked resolution of the swelling and the antibiotic was discontinued. None of these 748 patients required further antibiotic therapy. CONCLUSIONS: The duration of antibiotic therapy in most patients with acute dentoalveolar infections can safely be 2-3 days, provided that drainage has been established. It is not, therefore, necessary for the majority of patients to complete a 5-day course of antibiotics.

Abscess↗
PubMed1997

Scientific validity.

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Data Interpretation, Statistical↗
PubMed1997

Infective endocarditis and the dental practitioner: a review of 53 cases involving litigation.

OBJECTIVE: To review episodes of infective endocarditis involving dental procedures that have resulted in litigation and to determine if any clinical recommendations can be obtained. DESIGN: 13-year retrospective study. INTERVENTION: Patient records were analysed to identify the probable cause of infective endocarditis. All were judged to be caused by dental manipulations on the basis of dental procedure, cardiac pathology, infecting micro-organism and time between onset of infection and dental manipulation. MAIN OUTCOME MEASURES: Cases were analysed to check if appropriate national guidelines on antibiotic prophylaxis were followed. Status of patient dental records was also evaluated. RESULTS: Dental procedures implicated in infective endocarditis were exodontia (23), scaling (21), root canal therapy with extra-canal instrumentation (7) and minor oral surgery (2). No medical history was recorded in 10 patients. In a further 31 medical history was inadequate or out of date. Dentists involved with these cases failed to give prophylactic antibiotics (48), prescribed incorrect antibiotics (2), or gave antibiotics at inappropriate times (2). There was one episode of prophylaxis with amoxycillin failing despite it being given correctly. CONCLUSIONS: If litigation is to be avoided dental practitioners must keep accurate dental records, take an appropriate medical history that is kept up to date and adhere to national guidelines on antibiotic prophylaxis.

Adult↗
PubMed1997

Metabolic activation of aromatic amines by human pancreas.

Epidemiologic studies have suggested that aromatic amines (and nitroaromatic hydrocarbons) may be carcinogenic for human pancreas. Pancreatic tissues from 29 organ donors (13 smokers, 16 non-smokers) were examined for their ability to metabolize aromatic amines and other carcinogens. Microsomes showed no activity for cytochrome P450 (P450) 1A2-dependent N-oxidation of 4-aminobiphenyl (ABP) or for the following activities (and associated P450s): aminopyrine N-demethylation and ethylmorphine N-demethylation (P450 3A4); ethoxyresorufin O-deethylation (P450 1A1) and pentoxyresorufin O-dealkylation (P450 2B6); p-nitrophenol hydroxylation and N-nitrosodimethyl-amine N-demethylation (P450 2E1); lauric acid omega-hydroxylation (P450 4A1); and 4-(methylnitrosamino)-1-(3-pyridyl-1-butanol) (NNAL) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-oxidation (P450 1A2, 2A6, 2D6). Antibodies were used to examine microsomal levels of P450 1A2, 2A6, 2C8/9/18/19, 2E1, 2D6, and 3A3/4/5/7 and epoxide hydrolase. Immunoblots detected only epoxide hydrolase at low levels; P450 levels were <1% of liver. Microsomal benzidine/prostaglandin hydroperoxidation activity was low. In pancreatic cytosols and microsomes, 4-nitrobiphenyl reductase activities were present at levels comparable to human liver. The O-acetyltransferase activity (AcCoA-dependent DNA-binding of [3H]N-hydroxy-ABP) of pancreatic cytosols was high, about twothirds the levels measured in human colon. Cytosols showed high activity for N-acetylation of p-aminobenzoic acid, but not of sulfamethazine, indicating that acetyltransferase-1 (NAT1) is predominantly expressed in this tissue. Cytosolic sulfotransferase was detected at low levels. Using 32P-post-labeling enhanced by butanol extraction, putative arylamine-DNA adducts were detected in most samples. Moreover, in eight of 29 DNA samples, a major adduct was observed that was chromatographically identical to the predominant ABP-DNA adduct, N-(deoxyguanosin-8-yl)-ABP. These results are consistent with a hypothesis that aromatic amines and nitroaromatic hydrocarbons may be involved in the etiology of human pancreatic cancer.

Acetyltransferases↗
PubMed1997

Comparison of voriconazole (UK-109,496) and itraconazole in prevention and treatment of Aspergillus fumigatus endocarditis in guinea pigs.

Left-sided Aspergillus fumigatus endocarditis was established in the guinea pig heart by catheterization and inoculation with conidia via a tributary of the femoral vein. This animal model was used to compare the efficacy of the triazole antifungal agents voriconazole (UK-109,496) and itraconazole. In the prophylaxis experiments, voriconazole at a dosage of 10 mg/kg of body weight given intraperitoneally twice daily prevented A. fumigatus endocarditis in all but 1 animal (11 of 12 animals were cured). Itraconazole did not prevent Aspergillus endocarditis when it was given at the same dosage and by the same route (0 to 12 animals were cured). In the treatment experiments with 10 animals per group, voriconazole at 10, 7.5 and 5 mg/kg given orally twice daily for 7 days produced cure rates of 100, 70 and 0%, respectively. In contrast, itraconazole at 10 mg/kg given orally twice daily did not cure A. fumigatus endocarditis in the guinea pig. It is concluded that voriconazole is highly efficacious in the prevention and treatment of Aspergillus endocarditis in the guinea pig and is superior to itraconazole in these respects.

Animals↗
PubMed1996

Nystatin pastilles and suspension in the treatment of oral candidosis.

Clinical audit revealed that the treatment of oral candidosis was more successful with nystatin pastilles than with nystatin suspension. The purpose of this investigation was to determine the reasons for this observation. The concentration of nystatin needed to kill 49 consecutive clinical isolates of Candida albicans was measured. The isolates varied in cidal concentrations from 1.875 to 30 U/ml. The time taken to kill these isolates at their cidal concentrations was found to vary from 120 to 300 min. Volunteer studies showed that antifungal activity in the oral cavity was eliminated rapidly after the use of nystatin suspension. In contrast, the polyene could be detected for at least 5 hours after use of the nystatin pastille. The nystatin pastille can be expected to be more effective at killing Candida albicans than the suspension due to its persistent effects.

Antifungal Agents↗
PubMed1996

Oral endotoxin in healthy adults.

This article presents a study that measured oral endotoxin levels in healthy persons with the Limulus amoebocyte lysate microassay. Only young nonsmoking adults with a healthy dentition measured with the plaque index and a good level of oral hygiene based on a twice-daily (morning and evening) tooth-brushing regimen were admitted to this open study. Each person was required to provide two oral washings of 10 ml sterile saline solution 1 week apart. Only those volunteers without oral carriage of aerobic gram-negative bacilli were enrolled in the baseline study. A total of 15 healthy adults with a median age of 29 years (range, 25 to 43 years) were included in the trial. The mean plaque score of the group was 1.2 +/- 0.1. They all maintained a twice-daily tooth-brushing regimen unaltered throughout the sampling period. A total of 30 mouth rinses were studied. None of the samples yielded potential pathogens including aerobic gram-negative bacilli, Staphylococcus aureus and yeasts; a culturing technique based on preenrichment in nutrient medium was used. Data showed mean oral endotoxin levels of 20 ng per ml of mouth rinse; the aerobic E. coli endotoxin was used as the classical standard. This is equivalent to 1 mg of anaerobic endotoxin per ml of undiluted saliva after correcting for the 10 to 10(2) dilution factor of the mouth rinse itself and for the 10(3) times less sensitivity of anaerobic endotoxin in the Limulus amoebocyte lysate-assay. The discussion includes the physiologic and clinical benefit of the low endotoxicity of anaerobic gram-negative flora apart from the technical aspects of both culture and endotoxin assays used in the study.

Adult↗