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Biomedical subjects

M Wootton

Publications and source records attributed to M Wootton.

At least 19 recordsLinked to original sources

In vitro activities of Y-688, a new 7-substituted fluoroquinolone, against anaerobic bacteria.

The in vitro activities of Y-688, a new 7-substituted fluoroquinolone derivative, against 317 nonduplicate anaerobic isolates were determined. Eighty-five percent of the Bacteroides fragilis group (n = 89) were inhibited by < or = 2 mg of Y-688 per liter, while 78, 100, 89, and 98% of gram-negative bacilli (n = 135), gram-positive cocci (n = 59), and non-spore-forming (n = 58) and spore-forming (n = 51) gram-positive bacilli, respectively, were inhibited by < or = 1 mg of Y-688 per liter.

Anti-Infective Agents

Bay 12-8039, a new 8-methoxy-quinolone: comparative in-vitro activity with nine other antimicrobials against anaerobic bacteria.

The in-vitro activity of a new 8-methoxy-quinolone, Bay 12-8039, was assessed against 218 anaerobic bacteria. Ninety-eight per cent of strains belonging to the Bacteroides fragilis group (n = 65) were inhibited by < or = 2 mg/L of Bay 12-8039 whereas 97%, 94%, 94% and 100%, respectively, of Gram-negative bacilli (n = 93), non-sporing Gram-positive bacilli (n = 36), endospore-forming Gram-positive bacilli (n = 34) and Gram-positive cocci (n = 45) were also inhibited by < or = 2 mg/L. Eighty-three per cent of all anaerobes tested were inhibited by < or = 1 mg/L Bay 12-8039 and 99.5% by < or = 4 mg/L. When compared with ciprofloxacin, clinafloxacin, ofloxacin and trovafloxacin, Bay 12-8039 was more active than ciprofloxacin and ofloxacin, equipotent to trovafloxacin but not as active as clinafloxacin.

Anti-Infective Agents

A new time-kill method of assessing the relative efficacy of antimicrobial agents alone and in combination developed using a representative beta-lactam, aminoglycoside and fluoroquinolone.

A time-kill curve employing nine sampling times over 6 h was used to provide data which were then used to develop a theoretical (best-fit) curve. From the theoretical curve parameters describing the rate of kill (alpha), time from addition of antibiotic to initiation of killing (d) and a function of the degree of killing observed (Ym/Yo) were defined. The area-under-the-curve (AUC) was calculated from the theoretical curve. The variability of each parameter was assessed using a theoretical curve to fit the data from experiments done on three occasions and in triplicate. In terms of the parameters alpha, d, Ym/Yo and AUC, no synergy was demonstrated with combinations of piperacillin/tazobactam plus ciprofloxacin or gentamicin when compared with single antibiotics. The AUC represents the best summary parameter of a time-kill curve but should be supported by other parameters describing the best-fit curve.

Acinetobacter

The in-vitro activity of trovafloxacin and nine other antimicrobials against 413 anaerobic bacteria.

The in-vitro activity of trovafloxacin and nine other antimicrobials was determined for 413 non copy anaerobic clinical isolates. Trovafloxacin was the most active quinolone tested with an MIC90 of 0.5 mg/L against Gram-positive cocci (n = 75); MIC90 of 4 mg/L against Gram-positive bacilli (n = 151); MIC90 of 0.5 mg/L for Gram-negative cocci (n = 12) and MIC90 of 1 mg/L for Gram-negative bacilli (n = 175). Overall the MIC90 of trovafloxacin was 1 mg/L which was equivalent to co-amoxiclav and one dilution higher than that of imipenem. The other seven comparators, including clindamycin and metronidazole, had higher MIC90 values than trovafloxacin. Trovafloxacin is likely to have clinically useful activity against anaerobes from human infection.

Anti-Bacterial Agents

The bacterial DNA content of mouse organs in the Cornell model of dormant tuberculosis.

SETTING: The Cornell model of murine tuberculosis has proved useful for demonstrating and studying dormancy. However, it has not previously been used to investigate the molecular aspects of dormancy. OBJECTIVE: To obtain a profile of the amount of Mycobacterium tuberculosis DNA at various stages of the Cornell model. DESIGN: BALB/C mice were infected intravenously with 2.7 x 10(6) cfu M tuberculosis strain H37Rv; they were left for two weeks, treated for 14 weeks with isoniazid and pyrazinamide and left untreated for a further 14 weeks. Spleens and lungs at start of treatment and at 8, 12, 14, 18, 24 and 28 weeks thereafter were examined by culture, and DNA in tissue homogenates was quantitated by polymerase chain reaction (PCR) and dot blot hybridisation. RESULTS: Culture and quantitative PCR estimated initial bacillary content at about 10(7) per organ. Thereafter, organ cultures rapidly declined and were usually negative between 14 and 28 weeks. However, during this period quantitative PCR consistently estimated about 5.5 log10 bacilli equivalents in spleens and lungs. Dot blot hybridisation sensitive to about 10 ng bacillary DNA was usually positive pretreatment and occasionally during and after treatment, hence confirming the PCR results. CONCLUSIONS: There is persistence of significant quantities of M. tuberculosis DNA throughout the various stages of the model. This may represent dead bacilli, free DNA or dormant forms.

Animals

A critical assessment of the agar dilution chequerboard technique for studying in-vitro antimicrobial interactions using a representative beta-lactam, aminoglycoside and fluoroquinolone.

The agar dilution chequerboard technique of studying antimicrobial interactions was assessed by testing a representative beta-lactam (piperacillin/tazobactam), aminoglycoside (gentamicin) and fluoroquinolone (ciprofloxacin) against themselves, that is piperacillin/tazobactam plus piperacillin/tazobactam, gentamicin plus gentamicin and ciprofloxacin plus ciprofloxacin. In addition, combinations of piperacillin/tazobactam plus gentamicin or ciprofloxacin were also tested against Enterobacteriaceae and Acinetobacter spp. in triplicate. The agar dilution chequerboard technique did not reliably show addition when agents were combined with themselves, and there was also considerable variation when beta-lactam plus aminoglycoside or fluoroquinolone combinations when tested in triplicate. These observations, and problems with the design of the method, indicate that the chequerboard technique should be used only with adequate controls and replication, and then interpreted with extreme caution; ideally, it should not be used as a method of assessing antimicrobial interactions.

Acinetobacter

Simple method for production of internal control DNA for Mycobacterium tuberculosis polymerase chain reaction assays.

A simple method for the production of internal control DNA for two well-established Mycobacterium tuberculosis polymerase chain reaction assays is described. The internal controls were produced from Mycobacterium kansasii DNA with the same primers but at a lower annealing temperature than that used in the standard assays. In both assays, therefore, the internal control DNA has the same primer-binding sequences at the target DNA. One-microgram quantities of internal control DNA which was not contaminated with target DNA could easily be produced by this method. The inclusion of the internal control in the reaction mixture did not affect the efficiency of amplification of the target DNA. The method is simple and rapid and should be adaptable to most M. tuberculosis polymerase chain reaction assays.

DNA, Bacterial

Stevie.

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Dysgerminoma

The role of restraint and disinhibition in appetite control.

Fifty-six women classified according to their restraint and disinhibition scores, using Stunkard and Messick's (1985) Eating Questionnaire, participated in an experiment in which the proportion of carbohydrate in a prepared meal and the knowledge provided to them about its contents were varied. Measures were taken of their desire for food and their willingness to eat, as well as the total intake and the amount of carbohydrate and of protein they ate at an ad libitum test meal 4 hr later. While the results do not support the argument that laboratory-induced counter-regulatory eating can be attributed to disinhibition, they emphasize the usefulness of our experimental model which allows the interaction of dietary, cognitive and personality factors to be examined concurrently in investigations of appetite control.

Adult

Towards the prevention of eating disorders. Some preliminary findings from an empirical investigation.

The high incidence of disordered eating among female adolescents and young adult women has been noted in surveys carried out in Australia, the USA, New Zealand and the UK. While a critical feature that distinguishes those who go on to develop anorexia nervosa or bulimia nervosa is their sense of a loss of control over their eating, the psychological and nutritional concomitants of this loss of control have not been empirically investigated. Preliminary findings are described from an experimental study which is aimed at systematically investigating the relationship between dietary composition and consumatory patterns, hunger and satiety. The results are discussed in terms of the possible role of 'diet' in perpetuating the symptoms of bulimia nervosa and anorexia nervosa.

Adolescent

Urine mutagenicity as an indicator of exposure to dietary mutagens formed during cooking of foods.

Studies were undertaken with individuals fed fried bacon meals to determine whether fruit or vegetables, ingested along with bacon, modified uptake and subsequent excretion of bacon mutagen(s). Urinary mutagenic activity was significant in those who had consumed bacon or mixed bacon/vegetable or bacon/fruit meals within the previous 2 to 3 hr period. Although urine activity varied by a factor of 4 among 15 subjects who consumed different meals, there was no evidence from this investigation that fruit or vegetables contributed to the inherent variability in total urinary mutagenic activity. However, some differences in excretion kinetics may be attributable to vegetable or fruit supplements in mixed meals.

Animals

Mutagenic activity of heated potato/oil systems.

Mutagens detected with Salmonella typhimurium strain TA 98 in the presence of liver S9 mix were extracted from potato slices, but not pure potato starch, after frying in oil. No mutagenic activity was detected using strain TA 100, in the presence or absence of S9 mix with either fried potato slices or potato starch. Mutagenic activity was detected at frying temperatures of 140 degrees C and above. The mutagenic activity was limited to the outer portion of the fried potato slices and increased with frying time and temperature. Mutagenic activity ratios for extraction with both (NH4)2SO4/NH4OH and Na2SO4/NaOH were similar.

Food Contamination