Guidelines for the design and conduct of clinical trials on dentine hypersensitivity

Clinical trials on dentine hypersensitivity have been numerous and protocols varied. To date there is little consensus as to the conduct of studies on this poorly-understood yet common and painful dental condition. A committee of interested persons from academia and industry was convened to discuss the subject of clinical trials on dentine hypersensitivity and a consensus report is presented. A double-blind randomized parallel groups design is recommended, although cross-over designs may be used for the preliminary screening of agents. Subjects may have multiple sites scored. Sample size will be determined by estimating the variability in the study population, the effect to be detected and the power of the statistical test to be used. Subject selection is based on a clinical diagnosis of dentine hypersensitivity, excluding those with conflicting characteristics such as currently-active medical or dental therapy. The vestibular surfaces of incisors, cuspids and bicuspids are preferred as sites to be tested. A range of sensitivity levels should be included. Tactile, cold and evaporative air stimuli should be applied. Negative and benchmark controls should be incorporated. Most trials should last 8 weeks. Sensitivity may be assessed either in terms of the stimulus intensity required to evoke pain or the subjective evaluation of pain produced by a stimulus using a visual analog or other appropriate scale. The subject's overall assessment may be determined by questionnaire. Outcomes should be expressed in terms of clinically significant changes in symptoms. Follow-up evaluation is required to determine the persistence of changes. At least 2 independent trials should be conducted before a product receives approval.     

In vivo fluoride profiles at different sites of buccal and lingual enamel surfaces obtained by enamel biopsy of human maxillary first permanent molars in young adults

Twenty male volunteers, average age 24 years, participated in this study. Specimens were obtained by enamel biopsy using 5 microliters of 0.5 M HClO4 for 30 s. Using a regression curve, comparisons of fluoride concentrations were made at different depths. The fluoride concentrations (mean +/- SE) at a depth of 5 microns were highest in the distobuccal (1698 +/- 136), high in the mesiobuccal (1343 +/- 122), low in the distolingual (1119 +/- 107), and lowest in the mesiolingual sites (819 +/- 78). Of the interior enamels (> or = 10 microns in depth), the distobuccal site (1330 +/- 88 parts/10(6) F at 10 microns) had a higher-concentration than all other sites. The fluoride profiles were steepest to shallowest in the order: distobuccal, mesiobuccal, distolingual and mesiolingual. There were no correlations between the enamel fluoride concentrations and the fluoride concentration in parotid saliva. It was concluded that in vivo fluoride profiles of maxillary first molars reflect the wear of the tooth surface with age and the condition of dental plaque deposition, and, to some extent, the site-specific distribution of saliva between buccal and lingual surfaces.     

Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin

Immunization is a safe and cost-effective method to protect adult patients against many diseases, including hepatitis B, pneumococcal infections, and influenza. Despite this fact, only 10% to 40% of adults in the United States who would benefit have been immunized. Approximately 62% to 92% of patients who develop a disease preventable by vaccination have visited an outpatient clinic at least once in the 3 years preceding their illness. Efforts to educate providers about immunization guidelines have not increased immunization rates. In this report, we propose using the preanesthesia clinic as an alternative site to screen, identify, and immunize adults at risk. We also discuss three vaccines that could be offered to patients and analyze the efficacy of the vaccines.     

Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development

The photodynamic effects of temoporfin (meso-tetrahydroxyphenylchlorin, mTHPC) and merocyanine 540 (MC540) in murine myeloid leukemia M1 and WEHI 3B (JCS) cells were compared. The mTHPC was found to be more potent and selective. At a lethal dosage of 90% killing (LD90), only 1.3 microM of mTHPC and 4.2 kJ/m2 of light irradiation was required, which was a 20-fold lower drug concentration and 11-fold smaller light dose than that required when using MC540. Meanwhile, three times less, or 15%, of the coincubated erythrocytes were destroyed by mTHPC than by MC540. Confocal micrographs showed that both drugs accumulated diffusely inside the cytoplasm in a very similar fashion, but mTHPC induced a more extensive apoptosis in photosensitized JCS cells. For example, at LD90, mTHPC practically killed all JCS cells via apoptosis and cleaved the DNA to extremely small 150 base-pair fragments. In contrast, among the JCS cells killed by MC540, about 88% died via apoptosis and large DNA fragments were abundant. Relative to MC540, the ability of mTHPC to trigger large-scale and thorough apoptosis in leukemia cells may help explain its potency and selectivity.