Translational research in radiotherapy trials.
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Biomedical subjects
Publications and source records attributed to S McKeown.
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Described herein is the design and synthesis of indazolylaminopyridopyrimidines and quinazolines as inhibitors of the class 1 tyrosine kinase receptor family. Data is presented for N(4)-(1-benzyl-1H-indazol-5-yl)-N(6),N(6)-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine 3B. This compound inhibited EGFr and c-erbB-2 enzymes selectively over other kinases. It inhibited the proliferation of a range of tumour cell lines in vitro and the growth of BT474 xenografts in SCID mice.
Five hundred and twenty-five bp of mitochondrial control region were sequenced and analysed for 20 Acinonyx jubatus and one Felis catus. These sequences were compared with published sequences from another domestic cat, 20 ocelots (Leopardus pardalus) and 11 margays (Leopardus weidii). The intraspecific population divergence in cheetahs was found to be less than in the other cats. However variation was present and distinct groups of cheetahs were discernible. The 80 bp RS2 repetitive sequence motif previously described in other felids was found in four copies in cheetah. The repeat units probably have the ability to form secondary structure and may have some function in the regulation of control region replication. The two central repeat units in cheetah show homogenization that may have arisen by convergent evolution.
In reptile practice, most nutritional problems arise from improper husbandry, including poor feeding management and provision of imbalanced diets. Each reptile species has its own requirements for temperature and humidity, space and social interaction, lighting, and habitat components. Failure, to provide these requirements often results in failure to thrive and secondary nutritional disorders. Common dietary problems include deficiencies of energy, calcium, vitamin D3, vitamin A, and fiber.
This study was designed to evaluate the effectiveness of stress management training workshops within Zeneca Pharmaceuticals. The study was of cross-sectional design, comparing groups of workshop attendees and non-attendees. In addition, self-rated well-being scores of attendees were compared with results obtained pre-workshop and 2-3 months after the workshop. Employees participating in the study were drawn from the Manufacturing, Research and Development, Sales and Marketing sites of Zeneca Pharmaceuticals located in Cheshire, United Kingdom. Three hundred and ninety persons who had participated in stress management workshops since 1988 were matched for age, gender and department with an equal number of employees who had not attended stress management workshops. Outcome measures included self-rated well-being (as measured by the 30-question General Health Questionnaire), knowledge of company guidance on the management of stress in staff, and an assessment of coping strategies. Subjects who had not attended a stress management workshop were much more likely to have a poor understanding of the principles of management of stress in staff [odds ratio (OR) = 8.3; 95% confidence interval (CI) = 3.3-21.3] and more likely to have poor coping skills (OR = 2.8; CI = 1.3-6.1). However, mean scores for the two measures were similar in attendees and non-attendees. Self-rating of current well-being was strongly associated with the life-events score, but not related to workshop attendance. The study indicates that stress management training workshops reduce the prevalence of employees with a poor understanding of the principles of the management of stress in staff and with poor coping strategies. An improvement in the self-rated well-being observed shortly after the workshop was not sustained.
The dominant ideology of the premenstrual woman is that of a person who has no control over her moods, cognition and behaviour because of her fluctuating hormone levels. The social influence of this stereotype has been put forward as an explanation for discrepancies between retrospective and prospective accounts of premenstrual experiences. However, recent research has found that women can and do distinguish between their own experience and that of the stereotype. What their own experience is (positive as well as negative) was the question that we set out to answer in this study. Nine undergraduate women were interviewed about their menstrual cycle experiences. Using qualitative analysis of their subjective accounts, a clear distinction between self and other premenstrual experiences emerged. While the women did experience premenstrual symptoms, they considered them to be relatively minor in comparison to what they defined as premenstrual syndrome. Furthermore, none of them had previously considered any positive menstrual cycle related experiences but the management of menstruation was emphatically viewed as a 'hassle'. We conclude that women can and do distinguish their own experience from the premenstrual stereotype and this needs to be recognized in the treatment setting; there is a lack of positive discourse for the menstrual cycle which needs to be developed and more attention needs to be paid to menstrual management because it is of great concern to women but is currently not discussed openly.
Three triclosan-containing "multi-benefit" dentifrices were compared for clinical efficacy in reducing supragingival calculus formation following a dental prophylaxis. A total of 544 subjects completed a double-blind parallel-group clinical study using the Volpe-Manhold Index (VMI) to record severity and occurrence of supragingival calculus. The study design included a pre-test period where the calculus formation rate was measured in subjects brushing with a placebo dentifrice. Following a prophylaxis, subjects were stratified for age, gender and VMI scores and assigned to one of four treatments: 1) a dentifrice containing 5.0% soluble pyrophosphate/0.145% fluoride as NaF/silica abrasive/0.28% triclosan (hereafter PPi/TCS-comparable to Crest Complete dentifrice, Procter & Gamble, UK); 2) a commercial dentifrice containing 2.0% Gantrez acid copolymer/ 0.145% fluoride as NaF/silica abrasive/0.30% triclosan (hereafter Gan/TCS-Colgate Total dentifrice, Colgate-Palmolive Company, UK); 3) a commercial dentifrice containing 0.5% zinc citrate trihydrate/0.15% fluoride as sodium monofluorophosphate/silica abrasive/0.20% triclosan (hereafter Zn/TCS-Mentadent P dentifrice, Unilever, UK); and 4) a control dentifrice comprised of 0.145% fluoride as NaF/silica abrasive (hereafter Control). Subjects were instructed to use their assigned dentifrice at least twice per day and to brush as they do normally. Supragingival calculus formation was assesed at two and four months using site-specific and whole-mouth VMI indices for both calculus severity and occurrence. Following four months of use, the PPi/TCS dentifrice provided statistically significant reductions in calculus severity (22-23%) and occurrence (15%) as compared with the Control dentifrice. The Zn/TCS dentifrice also provided significant reductions in calculus severity (17-19%) and occurrence (12-13%) as compared with the Control. The Gan/TCS produced no statistically significant reductions in calculus formation (occurrence or severity) compared with the Control. The PPi/TCS dentifrice provided statistically significant reductions in calculus severity (15-21%) and occurrence (12-16%) as compared with the Gan/TCS dentifrice. These results support the clinical effectiveness of PPi/TCS and Zn/TCS dentifrices for the reduction of supragingival dental calculus formation following a dental prophylaxis.
A number of triclosan toothpastes are available which have been shown to benefit gingival health when compared to triclosan free control formulations. There have been few studies to compare such active products with conventional fluoride toothpaste products. The aim of this study was to compare, in home use, a triclosan product with conventional fluoride products already found to show slightly less plaque inhibition in a short term plaque regrowth study. The study was a single-blind, parallel design with a total of 129 healthy dentate volunteers (32 male, 97 female) who toothbrushed with one of 4 toothpaste products at home, twice a day over a period of 12 weeks. At the beginning of the trial, each volunteer was scored for plaque and gingivitis and then received a through prophylaxis. Each volunteer was allocated a toothpaste according to a predetermined randomisation scheme. The volunteers were re-examined after 6 and 12 weeks. The volunteers refrained from using any other oral hygiene products during the period of the trial. The toothpastes tested were two conventional fluoride toothpastes, a children's fluoride toothpaste and a triclosan/copolymer toothpaste. Results indicated that there were no overall significant treatment differences for either plaque index or gingival index and ordering of toothpastes was not possible. All volunteers' oral hygiene and gingivitis improved following the 6-week period and continued to improve to the 12th week. This is a feature of most oral hygiene trials and presumably arises from the initial prophylaxis and a Hawthorne response of improved toothcleaning by the subjects. It must be concluded from this study that in normal home use the triclosan/copolymer toothpaste provides oral hygiene and gingival health benefits no greater than achievable with conventional toothpaste products.
Toothpastes have been shown to have an antimicrobial activity both in vitro and in vivo; this activity variably translates into a plaque inhibitory effect in vivo. Commercially available toothpastes have a complex chemical make-up and some contain additional chemicals for which improved effects against plaque have been claimed. The aim of this study was to assess the plaque inhibitory properties of 5 commercially available toothpastes compared to a rinse of water over 4 days. The study was a randomised, single-blind, cross-over design balanced for residual effects. Volunteers were rendered plaque-free at each baseline and rinsed for 1 min, under the supervision of an assistant, 2x a day with the allocated mouthrinse or toothpaste slurry. At the end of the 4-day test period, the plaque was disclosed and measured by plaque index and plaque area. The plaque measurements indicated a significant difference between the toothpastes. The order of efficacy was Colgate Total, Crest regular, Crest Tartar, Colgate regular, Colgate 0-6 gel and water. This confirms previously reported data confirming the plaque inhibitory properties of certain toothpastes compared to water. These data indicate that the choice of control toothpaste with which to compare toothpastes formulated for plaque control is important and could influence conclusions drawn from clinical trials of such products.
In Senegal the generation of funds from the users of public health services in accordance with a strategy based on the Bamako Initiative is proving to be an extremely effective means of cost recovery and, in conjunction with management changes, is helping to improve the standard and scope of primary care.
Many compounds could be added to toothpaste to assist plaque inhibition, but ionic interactions can cause formulation difficulties. Moreover, the actual chemical action of a plaque inhibitory agent added to a toothpaste is difficult to assess when the product is used in the conventional manner, i.e., in addition to toothbrushing. The non-ionic antimicrobial triclosan has been incorporated in toothpastes and shown to have variable plaque inhibitory activity both alone and in conjunction with certain polymers or metal ions. Little is known of the efficacy of triclosan toothpastes compared to conventional fluoride toothpastes. The aim of this study was to compare a commercially available toothpaste containing 0.3% triclosan/co-polymer with a sodium fluoride toothpaste for chemical plaque inhibitory effects over a 4-day period. The study was designed to stratify the relative efficacy plaque inhibitory action of the products, comparisons were made with a positive control, chlorhexidine rinse and a negative control, saline. The study design was a randomised single blind crossover design balanced for first-order carryover. A total of 18 healthy, dentate volunteers participated in the study. On day 1 of each period the volunteers suspended toothcleaning and rinsed 2 x daily with the allocated mouthrinse or toothpaste slurry. On day 5, the plaque on the teeth was disclosed and scored by index and area. Increasing plaque scores were in the order chlorhexidine, triclosan toothpaste, fluoride toothpaste, and saline. Chlorhexidine was significantly more effective than all the other agents tested, and both toothpaste preparations were significantly better than the saline rinse. There was no significant difference between the two toothpaste rinses. Consistent with other studies the triclosan toothpaste offers only moderate plaque inhibitory properties when compared to a conventional toothpaste.
The efficacy of oral hygiene agents in preventing the accumulation of plaque from a zero baseline is conveniently evaluated in the 4-day plaque regrowth model. In many studies a panel of volunteers has been used to compare several agents according to a highly efficient Latin square based crossover design. Often chlorhexidine gluconate is included as a positive control; there is concern that the effect of this potent agent might persist for longer than the 3-day washout period often employed. To test this hypothesis of residual effect, we put together the evidence relating to possible carryover from 12 studies. The residual effect of chlorhexidine differs from that of an inert rinse such as saline or water. Consequently, a longer washout period, such as 10 days, is preferable. Studies omitting chlorhexidine are worth considering. Designs should be balanced for residual effects, at least from the preceding treatment period; several useful designs with this property are presented.
In a randomized prospective treatment study, 80 overdose patients (not requiring intensive psychiatric intervention) received either brief out-patient counselling or were returned to the care of their general practitioners with advice on management. There was little difference in outcome between the two groups. However, two sub-groups of patients benefited more from out-patient counselling than from general practitioner care, these were: (a) women, and (b) patients with dyadic problems. Counselling following overdoses should be focused on groups of patients such as these who are most likely to benefit from it. Further work is needed to identify treatment approaches that will help other groups who take overdoses, especially men.
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