On the value of research in health care.

This paper describes 3 important myths that reduce the political impact of academic research in healthcare and reviews data on the social return of such research. The myths are (i) scientists' interest in pursuing issues without concern for value to society; (ii) industry and private investors should fund more of society's basic research; (iii) Academic research can be improved by better administration. A recent study on return on investment in academic research in general is discussed as well as more specific studies on research related to healthcare. Examples include the BCG and Polio vaccines that today saves Norway more in healthcare costs than the entire public bill for drugs. Some factors that explain why research is undervalued are reviewed, notably rapid changes making benchmarking difficult, insufficient routines in accounting, changing goals, and unpredictable outcomes.

Effect of a combined chlorhexidine and NaF mouthrinse: an in vivo human caries model study.

Chlorhexidine (CHX) is probably the most widely used and the most potent chemical plaque inhibitory agent, whereas fluoride (F-) is the only truly accepted anticaries agent available at present. As they have discrete mechanisms of action, a combination effect of these agents on human dental caries may exist. The inhibitory effect of CHX on the formation of, and acid production in, plaque may reduce a relatively extreme cariogenic challenge sufficiently for it to be overcome by the local F- concentrations achieved by brushing or rinses. The aim of this study was to evaluate the possible caries inhibitory effect of combining 2.2 mM CHX mouthrinses used twice daily with daily 11.9 mM NaF rinses in an in vivo human caries model using plaque-retaining bands on premolars scheduled for extraction. Nine subjects (a total of 28 teeth) were fitted with the bands for 4 wk. Saliva and plaque samples were collected before and after the study period for bacterial cultures, and the tooth surfaces were analyzed by microradiography after careful tooth extractions. The combination of CHX and F- rinses resulted in enamel mineral loss only slightly higher than that observed in "sound" enamel and clearly less than with F- rinses alone. Both total plaque bacteria and Streptococcus mutans were reduced by CHX rinses, confirming the discrete mechanisms of action.

Copper in approximal plaque from conventional and non-gamma-2 amalgam restorations.

Differences in copper concentrations found in plaque adjacent to conventional compared with copper-rich non-gamma-2 amalgam fillings were evaluated. Plaque was sampled at baseline and up to 2 months after polishing of two to four fillings of each type of amalgam in six patients. Copper concentrations of several hundred ppm were found, with higher values in plaque sampled from copper-rich amalgam. However, the copper release from the copper-rich amalgam probably has very little influence on plaque ecology owing to a relatively low copper ion activity because of stable copper complexes in plaque.

Effect of a combination of copper and hexetidine on the acidogenicity and copper accumulation in dental plaque in vivo.

A double-blind crossover study on 4 adult volunteers was performed to evaluate the effect of hexetidine on Cu2+ accumulation in dental plaque as well as a possible enhanced effect of copper on inhibition of acid production in the presence of hexetidine. The experimental period was 5 days. No oral hygiene was allowed, and sucrose-containing chewing gum was used to enhance plaque formation during the test period. In order to evaluate the effect on pH, the test persons rinsed with a 15% glucose (w/v) solution on the 5th experimental day. Plaque pH values recorded before and 5 min after the rinse served as control values. One hour later the test persons rinsed with 10 ml of the test solutions for 1 min. Glucose rinses with pH measurements 5 min after the rinse were carried out 0, 3, and 7 h after the test agents were used. The combination of 1.0 mM copper and 2.0 mM hexetidine gave a significant (p less than 0.05) inhibition of acid production at all times compared both to the controls and to each of the test agents separately. Plaque samples were collected with a toothpick immediately before a 1-min rinse with 10 ml of the test solutions. Subsequent plaque samples were taken 5 min and 3 and 8 h after a rinse from corresponding tooth surfaces. Dry weight was estimated, the plaque bacteria digested by HNO3, and the amount of Cu2+ determined by atomic absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of a combination of copper and hexetidine on plaque formation and the amount of copper retained by dental plaque bacteria.

Zn++ in combination with hexetidine exerts a synergistic plaque inhibition. Studies in our laboratory on the mechanism of this effect suggested that Cu++ and hexetidine may have a similar combination effect. This hypothesis was tested in vivo on a human test panel in a double-blind crossover study. The amount of Cu++ retained by plaque bacteria in vitro was also evaluated. Seven volunteers rinsed with the solutions for 1 min twice daily for 5 days. The test solutions were H2O, 1.0 mM CuSO4, 2.0 mM hexetidine, and the last two in combination. During the test period no oral hygiene was allowed, and sucrose-containing chewing gum was used to enhance plaque formation. The plaque index scores after rinsing with the combination were significantly (p less than 0.05) lower than those of the other solutions. The effect of hexetidine on Cu++ retention in plaque bacteria was evaluated in plaque samples (n = 3) grown anaerobically overnight in PPLO medium. The bacteria were washed five times, digested in concentrated HNO3, and Cu++ determined by atomic absorption. The presence of hexetidine resulted in a significantly greater amount of Cu++ retained by bacteria at all CuSO4 concentrations. It is suggested that the nonpolar nature of the hexetidine molecule enables Cu++ bound to hexetidine to pass into the bacterial cell. Within the cell, Cu++ can interfere with bacterial metabolism, giving a reduction in plaque growth.

Dissolution of calcium fluoride tablets in vitro and bioavailability in man.

The dissolution rate of CaF2 tablets in vitro and the degree of F absorption in vivo after tablet intake in man were investigated. 50% of total F was released in 0.1 N HCl after 45 min whereas virtually no release was seen in H2O or in 0.2 M PO4-buffer pH 6.8. In spite of the modest release of F in simulated gastric juice in vitro no F absorption as judged from the plasma fluoride concentration curve was seen within 6 h after intake of 4 mg F as CaF2 tablets.

Factors affecting retention of Cu in the human oral cavity after mouth rinses.

Retention of Cu in the mouth after rinses with aqueous solutions of CuSO4 was measured by atomic absorption spectrophotometry. The retained amount of Cu exhibited a linear relationship against the concentration of the rinsing solution in the range tested. Approximately one third of the Cu retained after a 60 s rinse was retained within the first 15 s, and about 75% within 30 s. Retention of Cu was only little affected by the pH of the rinsing solution in the range from 2.0 to 5.7, being reduced by about 50% at pH 9.0. However, variations in cupric ion activity rather than pH per se could explain these effects. A mutual reduction in retention of either metals was seen when Cu and Zn were applied simultaneously.

Effect of topical application of stannous fluoride, stannous chloride and stannous tartrate on rat caries.

Topical application of 10 mM aqueous solutions of stannous fluoride inhibited caries in rats to a higher degree than 20 mM sodium fluoride, although the difference was not statistically significant. Furthermore, stannous fluoride reduced the number of Strep. mutans in plaque significantly; stannous ions have an antibacterial effect. Stannous chloride and stannous tartrate did not reduce caries in the rats, probably because of the low concentrations of available stannous ions in these solutions at low pH. The high concentration of stannous ions in solutions of stannous fluoride is probably partly due to the reduced hydroxide formation resulting from the buffering effect of HF formed at low pH in this solution.

Some aspects of the dynamics of Cu and Zn retained in plaque as related to their effect on plaque pH.

The effect of glucose on acid production in dental plaque was measured in vivo after oral rinses with CuSO4 (1.0 mM) or Zn (Ac)2 (20 mM) and compared with the retention of the metals. Plaque samples were analyzed for copper and zinc by neutron activation analysis. A rinse with the cooper salt solution significantly depressed acid formation in plaque for a period of 6 h whereas a rinse with the zinc solution was effective for 2 h. Plaque concentrations of the metals increased from less than 75 p.p.m. to more than 1000 p.p.m. 2 h after a rinse with the metal salts. Twelve hours after a rinse the mean plaque concentrations were 190 p.p.m. Cu or 358 p.p.m. Zn respectively. Reducing the pH of the copper sulfate solution from 5.7 to 2.0 yielded lower Cu concentrations in plaque 2 h after a rinse, indicating lower initial retention. The results clearly demonstrate a high and long lasting retention of metal ions in dental plaque and their biological effect in this environment.

Retention of Cu and Zn in the oral cavity following rinsing with aqueous solutions of copper and zinc salts.

Retention of Cu and Zn in the mouth after rinses with known volumes of aqueous solutions of the metal salts was measured by atomic absorption. The mean amounts retained in 10 subjects were 0.02 mg Cu and 0.22 mg Zn. These values represent approximately 31% of the Cu and 15% of the Zn originally in the rinse. The intraindividual variation (s.d.), estimated by three mouthrinses at weekly intervals in three subjects averaged 2.1% for Cu and 2.3% for Zn. Following a rinse the salivary concentration of Cu and Zn decreased rapidly during the first 4 h, approaching prerinse levels.