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Biomedical subjects

R Newcombe

Publications and source records attributed to R Newcombe.

At least 19 recordsLinked to original sources

Glucocorticoids exacerbate kainic acid-induced extracellular accumulation of excitatory amino acids in the rat hippocampus.

Glucocorticoids (GCs) compromise the ability of hippocampal neurons to survive various insults, and do so, at least in part, by exacerbating steps in the glutamate/N-methyl-D-aspartate (NMDA)/calcium cascade of damage. As evidence, GCs impair uptake of glutamate by hippocampal astrocytes, the GC endangerment of the hippocampus is NMDA receptor dependent, and GCs exacerbate kainic acid (KA)-induced calcium mobilization. These observations predict that GCs should also exacerbate KA-induced accumulation of extracellular glutamate and aspartate. To test this, adrenalectomized rats were given replacement GCs in either the low or high physiological range. Three days later, rats were anesthetized and 1 mM KA was infused through a dialysis probe placed in the dorsal hippocampus. Extracellular amino acid concentrations in the dialysate were then assessed by HPLC. After KA infusion, high-GC rats (30 +/- 3 micrograms/dl) had significantly elevated concentrations of glutamate and aspartate compared with low-GC rats (all less than 0.95 micrograms/dl). The glutamate accumulation was due to GCs raising pre-KA concentrations, whereas the aspartate accumulation was due to GCs exacerbating the KA-induced rise. Glutamine concentrations were unaffected by KA, whereas the high-GC regimen elevated glutamine concentrations both before and after KA. Taurine concentrations rose after infusion of KA, but were unaffected by GC regime, whereas alanine concentrations were unaffected by either manipulation. Serine concentrations were unaffected by KA, but were depressed both before and after KA in high-GC rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids

The effects of antimicrobial acrylic strips on the subgingival microflora in chronic periodontitis.

This study investigated the effects of root planing and/or the placement of acrylic strips containing chlorhexidine, metronidazole or tetracycline on the composition and antimicrobial susceptibility of the subgingival flora in chronic periodontitis. 101 periodontal pockets from 73 patients were entered into 6 treatment groups which were, chlorhexidine, metronidazole or tetracycline strips, root planing, root planing followed by metronidazole strips and a control, no treatment group. Total anaerobic counts and anaerobe/aerobe ratios were estimated from samples taken before treatment and 1, 2, 4, 8 and 12 weeks after treatment. In addition, a more detailed analysis of the effects of the treatments on the subgingival flora was carried out on 12 pockets in 12 patients. Tetracycline strips, metronidazole strips and root planing and metronidazole strips were more effective than chlorhexidine strips in causing reductions in total anaerobic count and anaerobe/aerobe ratio. However, the changes in microbial parameters rebounded to approach baseline levels 4 weeks after treatment. Chlorhexidine caused no detectable changes in the composition of the subgingival microflora, while metronidazole had a variable effect. Tetracycline appeared to effect major shifts in the composition of the microflora of treated pockets but caused a marked selection of tetracycline-resistant organisms.

Acrylic Resins

Thyrotropin response to thyrotropin-releasing hormone in elderly patients with and without acute illness.

The response of thyrotropin (TSH) to thyrotropin-releasing hormone (TRH) was measured in 70 clinically euthyroid elderly patients who were acutely ill and in 70 age- and sex-matched euthyroid controls who were free of acute disease. The incremental TSH response (delta TSH) was often blunted (less than 2 mU/l) in both groups, though more often in those with acute illness (30%) than in those without (19%). However, in patients from both groups who had a blunted delta TSH, there was often a substantial proportional rise in TSH. A substantial proportional TSH rise may be useful in differentiating between genuine thyroid disease and euthyroid sick syndrome in elderly patients with a blunted delta TSH.

Acute Disease

The effect of some chlorhexidine-containing mouthrinses on salivary bacterial counts.

A number of chlorhexidine mouthwashes are available commercially which differ in formulation and regimen of use. As a comparative measure of antimicrobial persistence, this study evaluated the effect of 4 chlorhexidine mouthwash formulations on salivary bacterial counts after a single rinse. The study was a randomised single-examiner blind 5-way crossover investigation employing a panel of 10 young healthy human volunteers. The 0.12% and 0.2% commercial formulations when rinsed according to the respective manufacturers instructions produced similar large and prolonged reductions in salivary bacterial counts during the 7-h period. A 0.1% formulation also commercially available produced minimal effects on salivary bacterial counts and was little different to the saline rinse. A reformulated 0.1% rinse, not commercially available at the time of the study, produced significant salivary bacterial count reductions over the 7-h period albeit to a lesser degree of magnitude than to the 0.2% and 0.12% rinses. The results were consistent with comparative plaque inhibitory studies of the formulations and suggest that the method is a quick and simple way of screening products for antimicrobial and antiplaque potential.

Adult

Triclosan and sodium lauryl sulphate mouthwashes (I). Effects on salivary bacterial counts.

A number of commonly used toothpaste ingredients, such as detergents, possess not inconsiderable antimicrobial activity. Additionally, specific ingredients including triclosan are now added to toothpastes to enhance such activity and to improve plaque inhibition. To date, there have been few studies of the antimicrobial properties in vivo of individual toothpaste ingredients. Most investigations have evaluated the whole toothpaste product. Persistence of antimicrobial action in vivo has been shown to relate to potential plaque inhibitory action. The aim of this study was to compare the magnitude and duration of salivary bacterial count reductions produced by a single rinse of 0.2% triclosan, 1% sodium lauryl sulphate (SLS) and 0.2% chlorhexidine mouthwashes. 16 volunteers took part in a single-blind latin-square randomised crossover designed study with balanced residual effects. Before and for time periods up to 420 min following rinsing with the allocated mouthwashes, saliva samples were obtained and processed for total anaerobic counts. With the exception of the saline control rinse, the 3 test solutions produced considerable reductions in bacterial counts which remained significant to 3 h for triclosan and 7 h for SLS and chlorhexidine. However, at most time periods after baseline, the effects of chlorhexidine were significantly greater than triclosan and SLS. Overall, SLS had significantly greater effects than triclosan. Incremental values from 30 min post rinsing were always positive for SLS and triclosan, indicating bacterial recovery, whereas these values were negative for chlorhexidine. The results indicate that triclosan and SLS provide some persistence of antimicrobial activity in the oral cavity when used at relatively high dose compared to a toothpaste vehicle.

Adult

Seasonal variation and the results of the dexamethasone suppression test.

There is controversy over the presence of a circannual rhythm in cortisol values in samples provided by depressed patients after a standard dexamethasone suppression test (DST). Post-DST cortisol values from patients admitted to an acute psychiatric ward over a 2-year period have therefore been analysed by appropriate statistical tests. No evidence was found for significant seasonal variation.

Depressive Disorder

Reporting cervical intra-epithelial neoplasia (CIN): intra- and interpathologist variation and factors associated with disagreement.

Eight histopathologists, based at different hospitals, who had previously examined 100 consecutive colposcopic cervical biopsies were circulated with the results of the initial study. The slides were then 'reblinded' and re-examined by the pathologists who, as before, assigned them into one of six diagnostic categories. The degree of interpathologist agreement for the seven observers who returned usable responses was characterized by kappa statistics and compared to the corresponding figures for the same observers from the previous study. Although some of the observers showed significant alterations in their diagnostic practices there was persistent poor agreement for CIN 1 and 2, mediocre agreement for CIN 3 and excellent agreement for invasive carcinoma. Intra-observer agreement was consistently better than inter-observer agreement for each of the diagnostic categories. Significant differences were found among observers in the degree of intra-observer variability. The 20 cases in which there was most disagreement were re-examined by one of the authors who compared these with 20 biopsies which caused little disagreement. Disagreement was considered to be associated with florid papilloma-virus changes, basal cell hyperplasia and severe inflammation in varying combinations. On the basis of these findings we suggest changes in the terminology of CIN lesions.

Carcinoma in Situ

The effect of triclosan, stannous fluoride and chlorhexidine products on: (I) Plaque regrowth over a 4-day period.

A number of substances have been incorporated into toothpastes or gels to inhibit plaque regrowth. The aim of this study was to evaluate triclosan and stannous fluoride products for plaque inhibitory properties by comparison with a chlorhexidine or saline rinse and a control product which was a conventional commercially available toothpaste. In a blind 8 cell cross-over study, 15 volunteers rinsed 2 x a day for 4 days with slurries of the products or the saline and chlorhexidine solutions. No other form of oral hygiene was performed and plaque regrowth from a zero baseline was recorded by plaque score and plaque area. Plaque regrowth was significantly less with the chlorhexidine rinse and significantly greater with the saline rinse compared to the toothpaste and gel products. No significant differences were found between the test and control products. The results again demonstrate that commercially available toothpastes have plaque inhibitory effects which so far appear difficult to improve upon by the addition of specific ingredients, in this case stannous fluoride or triclosan. Commercially available products of known activity would appear useful benchmarks for comparison of experimental formulations.

Adult

The effect of triclosan, stannous fluoride and chlorhexidine products on: (II) Salivary bacterial counts.

A previous study demonstrated that triclosan and stannous fluoride containing oral hygiene products reduced plaque regrowth compared to saline but were not more effective than a conventional commercial fluoride/anionic detergent toothpaste. To further understand these results, this study measured the persistance of antimicrobial activity of the same products by recording the duration of salivary bacterial count reductions following a single exposure to each product. Comparison was also made with a chlorhexidine rinse as the positive control. From a panel of 16 volunteers, in an 8-cell randomised cross-over designed study, salivary bacterial counts were recorded at baseline and to 420 min. All test and control products were significantly more effective than saline and significantly less effective than chlorhexidine at suppressing bacterial counts. Unlike chlorhexidine, evidence of bacterial recovery was apparent after the 30-min sampling time. There were essentially no significant differences between the test and control products, although the stannous fluoride toothpaste performed marginally better than other products. The findings are consistent with the plaque regrowth results previously obtained and again demonstrate to date that it is difficult to surpass the antimicrobial and plaque inhibitory properties of conventional commercially available toothpastes by the addition of antimicrobial agents such as triclosan and metal salts.

Adult

The effects of 0.5% chlorhexidine and 0.2% triclosan containing toothpastes on salivary bacterial counts.

A number of antimicrobial compounds could be incorporated into toothpastes to enhance plaque inhibitory effects. However, the number of possible formulations is immense and makes clinical testing in plaque and gingivitis studies difficult. In this study, the effects on salivary bacterial counts of a number of chlorhexidine and triclosan toothpastes was evaluated as a predictor of persistence of antimicrobial action in the mouth. The study was a supervised, randomised 15-way crossover study employing 10 healthy human volunteers. All toothpastes were brushed for 1 min and comparison made with a 0.2% chlorhexidine rinse. The latter produced a large drop in salivary bacterial counts to the end of the 7-h study period. The toothpastes decreased salivary bacterial counts and all but two had notably more effect than a water brushing. No toothpaste showed a significant persistence of antimicrobial effect beyond 5 h. In the light of available plaque inhibition data for the toothpastes, persistence of antimicrobial activity beyond 5 h will be necessary for a clinical effect on plaque and gingival health. The method appears to be a simple and rapid screening technique for products formulated to enhance plaque inhibition mediated through an antimicrobial action.

Adult

Comparative effects of toothpaste brushing and toothpaste rinsing on salivary bacterial counts.

The persistence of antimicrobial action of compounds and formulations in the mouth can be demonstrated by recording the magnitude and duration of the reduction of salivary bacterial counts following a single application. Such measures of substantivity appear to correlate with the plaque inhibitory properties of antimicrobial agents. For toothpastes, studies on the short-term inhibition of plaque formation use a number of delivery methods to measure the direct effect of the preparation divorced from toothbrushing. Such methods include paste slurries, paste in trays or cap splints. This study determined whether toothbrushing with a toothpaste produced the same effects on salivary bacterial counts compared to rinsing with a slurry. A group of 24 volunteers brushed or rinsed with a slurry of a commercial toothpaste. Each regimen was repeated twice on 4 separate days by all volunteers and salivary bacterial counts recorded at baseline and time periods to 7 hours. There were no significant differences between brushing or slurry rinsing on salivary bacterial counts and each method produced reproducible effects. This supports the use of the slurry method where the direct plaque inhibitory action of an antimicrobial toothpaste is to be assessed; and indicates that both methods equally make available and activate the relevant ingredients in formulations.

Adult

Structural mechanisms of trabecular bone loss in man.

The relationship between trabecular thinning and loss of connectedness of the trabecular bone pattern has been studied in iliac crest bone samples from 89 normal subjects in order to determine the structural mechanisms underlying age-related bone loss. Trabecular width and structure were quantitatively assessed using computerized techniques. Highly significant negative correlations were found between the mean trabecular plate thickness and number of free ends/mm2 both in males (r = -0.571) and in females (r = -0.667) (P less than 0.001). Mean trabecular plate thickness also showed significant negative correlations with other structural indices indicating reduced connectedness, whereas positive correlations were found with those indices representing preservation of connectedness. Examination of the relative frequency of trabecular widths less than 100 microns revealed that only 2-5% of the trabecular surface would be susceptible to erosion by a resorption cavity of normal depth. These results indicate that trabecular thinning and erosion are interdependent processes in age-related bone loss. Since only a small percentage of the trabecular surface is susceptible to erosion, and resorption cavities normally occupy only 1-5% of the total trabecular surface, these findings imply that the site of activation of new BMUs may not be randomly distributed but may instead be preferentially located at sites of lower trabecular width.

Adult

Thyroid function tests in elderly patients with and without an acute illness.

Thyroid function was assessed by measurement of free thyroid hormones and thyrotrophin (TSH) in 78 acutely ill elderly patients and in a control group without acute illness. Abnormal results with any test were more frequently found in the acutely ill group than in controls. In particular, abnormal TSH values were found in 40% of the acutely ill group and in only 8% of controls (p less than 0.001). Seven acutely ill subjects had very low TSH levels (less than 0.04 mU/l) and a blunted response to thyroid-releasing hormone (TRH). With few exceptions these abnormalities could not be attributed to thyroid disease. This suggests that pituitary TSH secretion can be impaired in euthyroid sick old people. High sensitivity TSH assays may therefore be inappropriate as first-line tests of thyroid function, at least in this select group.

Acute Disease

Studies on the effect of toothpaste rinses on plaque regrowth. (I). Influence of surfactants on chlorhexidine efficacy.

A number of compounds have been added to toothpastes to inhibit plaque regrowth. The inclusion of cationic antiseptics, such as chlorhexidine, poses formulation difficulties because of interactions with other ingredients particularly anionic detergents. More recently, Triclosan/zinc citrate formulations have been shown effective plaque inhibitors. The aim of this study was to compare a commercially available 0.2% Triclosan/0.5% zinc citrate toothpaste with a number of experimental 0.5% chlorhexidine/detergent toothpastes for effects on plaque regrowth over 4 days. Subjects rendered plaque free at each baseline rinsed twice a day with toothpaste slurries and disclosed plaque was scored at the end of each period. All toothpastes significantly reduced plaque by comparison with a control toothpaste, but were significantly less effective than a 0.2% chlorhexidine rinse. Some significant differences in favour of one chlorhexidine toothpaste were noted but these were small in magnitude. Whether the plaque inhibition obtained with Triclosan/zinc citrate toothpaste was greater than would be expected from other commercially available preparations cannot be determined from this study and is the subject of a further investigation.

Adult

Studies on the effect of toothpaste rinses on plaque regrowth. (II). Triclosan with and without zinc citrate formulations.

Encouraging findings have been reported for the effects of Triclosan/zinc citrate toothpastes on plaque regrowth and in some studies gingival health. To date, commercially-available toothpastes contain 0.2% Triclosan with or without 0.5% zinc citrate. The aim of this study was to evaluate the effects on 4-day plaque regrowth, of a number of 0.2% Triclosan toothpastes with or without zinc citrate. All of the toothpastes contained varying levels of anionic detergent sodium lauryl sulphate and were compared with a commercially available toothpaste without Triclosan or zinc citrate and a 0.2% chlorhexidine mouthrinse. The toothpastes were used as slurry twice a day and plaque regrowth scored by area and the criteria of the debris index. Plaque inhibition was significantly greater with the chlorhexidine mouthrinse than with all of the toothpastes. There were no significant differences in plaque scores between any of the toothpastes. It would appear that at the concentration of 0.2% Triclosan with or without 0.5% zinc citrate provides little if any additional benefit to plaque inhibition to that produced by a conventional toothpaste containing sodium lauryl sulphate.

Adult

Comparison of the effect of toothpastes containing enzymes or antimicrobial compounds with a conventional fluoride toothpaste on the development of plaque and gingivitis.

Many toothpastes have been formulated over recent years to contain antimicrobial compounds with the aim of preventing or reducing plaque, calculus, gingival inflammation or dental caries. For many, if not all of these toothpastes, it has yet to be proven whether they are significantly better at reducing plaque and gingivitis than conventional toothpastes, for which no such therapeutic effects have been claimed. This 12-day, incomplete block designed, cross-over study compared the development of plaque and gingivitis following rinsing with toothpaste slurries containing the following active ingredients: (1) hexetidine/zinc citrate, (2) 0.2% triclosan, (3) amyloglucosidase/glucose oxidase, (4) sodium fluoride/sodium monofluorophosphate (NaF, MFP). By the 8th day of the study, a significant difference in gingival crevicular fluid (GCF) and GI was found between the groups. By day 12, however, no significant difference in plaque index and gingival inflammation was found between the 4 toothpastes, although plaque area was significantly reduced with the hexetidine/zinc citrate paste when compared to the conventional fluoride paste. It was concluded that the active ingredients added to the toothpastes evaluated in this study provided little or no more additional benefit to oral hygiene and gingival health than could be achieved with a conventional fluoride toothpaste.

Adult

Toothpastes containing 0.3% and 0.5% triclosan. I. Effects on 4-day plaque regrowth.

Triclosan has been added to toothpaste formulations, alone or with zinc salts, to reduce plaque regrowth. The most encouraging results have been obtained with triclosan/zinc formulations particularly at the higher concentrations of one or both agents. Formulations containing 0.2% triclosan alone have shown less promise and the aim of this study was to measure plaque regrowth over 4-day periods with the use of 0.3% and 0.5% triclosan toothpastes with and without the addition of a copolymer, polyvinyl methyl ether maleic acid (PVM/MA) and to compare the findings with a conventional fluoride/anionic detergent based toothpaste and a 0.2% chlorhexidine mouthrinse. The method was a no oral hygiene randomized 6 times crossover study using the toothpaste slurry rinsing method. Plaque was recorded by a plaque index and by area. Three of the four triclosan toothpastes reduced plaque regrowth significantly compared with the placebo, with no significant differences among the triclosan toothpastes. Plaque scores were always significantly lower with the chlorhexidine mouthwash compared to all toothpastes. The results suggest that at 0.3% to 0.5% triclosan alone or with a copolymer toothpaste may be a benefit to oral hygiene, but whether this is sufficient to affect gingival health requires further clinical evaluation. Further research would also appear indicated to determine optimal levels for the copolymer concentrations in toothpastes.

Adult