Biomedical subjects

Richard A Reinhardt

Publications and source records attributed to Richard A Reinhardt.

12 recordsLinked to original sources

PubMed2006

Drug delivery strategies for common orofacial diseases.

There are many types of diseases associated with the oral cavity. As an adjunct to professional oral dental care, various drug delivery systems have been developed to improve the treatment or prevention of these diseases. In this manuscript, the current status of drug delivery strategies for these common orofacial diseases is reviewed. Biomineral-binding drug delivery and on-demand drug release are suggested to be considered in the future design of drug delivery systems for orofacial diseases. Apparently, this research field deserves much more attention from both pharmaceutical scientists and dental health professionals.

Bone and Bones↗

PubMed2005

Relationship between gelatinases and bone turnover in the healing bone defect.

PURPOSE: The aim of this pilot study was to determine the relationship between gelatinase (MMP-9 and MMP-2) markers of soft tissue inflammation/turnover at the bone/soft tissue interface and bone turnover (osteocalcin [OC], pyridinoline cross-linked carboxyl-terminal telopeptide of type 1 collagen [ICTP], and bone fill) during healing of an alveolar bone defect. MATERIALS AND METHODS: Ten subjects undergoing oral surgery had a 5 x 5-mm trephine defect created on an edentulous ridge and were sampled at the bone/soft tissue interface at baseline (prior to flap reflection), 2 weeks and 12 weeks postsurgery, using a novel bone wash device. Recovered irrigants were analyzed for MMP-9 and MMP-2 by gelatin zymography, OC and ICTP with radioimmunoassays, and albumin (ALB; to normalize markers for blood content) with a sandwich enzyme-linked immunosorbent assay. Bone fill at 12 weeks was analyzed by radiographic absorptiometry. RESULTS: All markers of enzymatic activity and bone turnover varied significantly across time (P < or = .03), with bone turnover markers OC and ICTP decreasing between baseline and 2 weeks, and MMP-9 and MMP-2 increased. Measures generally returned to near baseline levels after 12 weeks. MMP-9 versus MMP-2 (r = 0.97, P < .0001) and OC versus ICTP (r = 0.38, P = .048) were correlated with each other, while MMP-9 and MMP-2 were negatively correlated with ICTP (r = -0.48, P = .011 and r = -0.62, P = .006, respectively). MMP-9 was negatively correlated with subsequent bone fill (r = -0.63, P = .07). CONCLUSIONS: Bone wash sampling showed that gelatinase activity at 2 weeks following creation of an alveolar defect appeared to decrease bone turnover and eventual bone fill, suggesting benefits for anti-MMP therapy during wound healing.

Alveolar Bone Loss↗

PubMed2005

Local simvastatin effects on mandibular bone growth and inflammation.

BACKGROUND: Simvastatin has been shown to increase bone growth when applied topically to murine bone; however, it causes considerable soft tissue inflammation at high doses (2.2 mg), making future clinical use problematic. This study evaluated the effect of lower simvastatin doses and cyclooxygenase (COX) synthase inhibitors on tissue inflammation and bone growth in rats and gene expression in mice. METHODS: Adult female rats were untreated or treated with a single dose of 0.1, 0.5, 1.0, 1.5, or 2.2 mg simvastatin in methylcellulose gel in a polylactic acid membrane (SIM) on the lateral aspect of the mandible. The contralateral mandible side was implanted with methylcellulose gel/polylactic acid membrane alone (GEL), and five rats in each dose pairing were evaluated histomorphometrically after 3, 7, and 24 days. Subsequent rats were similarly treated with 0.5 mg simvastatin (optimal dose) and daily intraperitoneal injections of COX-2 inhibitor (NS-398; 1 mg/kg x 7 days; N = 16), general COX inhibitor (indomethacin; 1 mg/kg x 7 days; N = 16), or no inhibitor (N = 10) and evaluated histomorphometrically after 7 or 24 days by analysis of variance (ANOVA). Gene arrays were also used to evaluate osteogenic gene expression from 0.5 mg simvastatin in murine calvaria (N = 12). RESULTS: There was a 45% increase in bone area with 0.5 mg simvastatin versus gel control (P <0.001; similar to the 2.2-mg dose), and clinical swelling was reduced compared to the high simvastatin dose (P <0.05). The 0.1-mg simvastatin dose failed to stimulate significant bone growth. NS-398 and indomethacin reduced inflammation and bone growth. Simvastatin significantly upregulated procollagen, fibronectin, and matrix metalloproteinase-13 genes. CONCLUSION: Reducing the simvastatin dose from 2.2 to 0.5 mg reduced inflammation to a more clinically acceptable level without sacrificing bone-growth potential, but COX-associated inflammation appears to be necessary for in vivo bone growth.

Animals↗

PubMed2005

Comparison of irrigation to floss as an adjunct to tooth brushing: effect on bleeding, gingivitis, and supragingival plaque.

OBJECTIVE: The purpose of this twenty-eight day, randomized, single-blind clinical trial was to assess the efficacy of the addition of daily oral irrigation to both power and manual tooth brushing, compared to a traditional regimen of manual tooth brushing and flossing, to determine which regimen had the greatest effect on the reduction of gingival bleeding, gingivitis, and supragingival plaque. METHODOLOGY: The study was designed for a total of 105 subjects to participate in a twenty-eight day trial, with 35 subjects randomly assigned to one of three groups: Group 1-manual toothbrush and floss; Group 2-manual toothbrush and dental water jet; and Group 3-sonic toothbrush and dental water jet. All subjects received written and verbal instructions for using their regimens. Subjects were asked to brush for a timed two minutes, twice per day, with the brush and the dentifrice provided, and to refrain from using any additional oral hygiene aids. Subjects using the dental water jet were instructed to use the water jet on a medium setting, irrigating once per day with 500 ml of luke warm water. Subjects using the dental floss were instructed to use the floss once daily. Subjects were examined by two calibrated examiners, and data were collected at baseline (BSL), 14 days (D14), and 28 days (D28). Subjects were asked to abstain from any oral hygiene for 12 hours prior to each study visit. Subjects were scored using the Carter and Barnes Bleeding Index, Löe and Silness Gingival Index, and the Proximal/Marginal Plaque Index. Mean scores on the three indices for the three groups were used for statistical analysis at each time point. Additionally, the means were used for comparisons as change from baseline and percent change from baseline at D14 and D28. The significance of percentage change in each index from baseline to D14 and D28 was evaluated using a one-tailed t-test. Significant differences are reported at alpha < or = 0.05 for these planned group comparisons. RESULTS: Thirty-one subjects in Group 1, 32 subjects in Group 2, and 32 subjects in Group 3 completed the study. Bleeding Index: Groups 2 and 3, the irrigation groups, were statistically significantly more effective than Group 1 in reducing the bleeding index at D14 and D28, whether measured by mean reduction or percentage reduction. Gingival Index: At D14, both irrigation groups demonstrated a statistically significantly greater reduction in the gingival index compared to brushing and flossing for the facial surfaces. There was no significant difference between groups for the lingual surface at D14. At D28 there was a significant difference between Groups 1 and 2 for both the facial and lingual surfaces. Plaque Index: There was one significant difference between groups for the plaque index measured on the lingual surfaces. The manual toothbrush and floss were less effective than the sonic toothbrush and irrigation. Group 3 was also significantly better than Group 1 in reducing the plaque index on the facial surfaces at both D14 and D28. On plaque percentage reduction on the facial surface, Group 2 was significantly better than Group 1 at D14. There was no statistical difference between Group 1 and Group 2 at D28. CONCLUSION: The results of this clinical trial indicate that when combined with manual or sonic tooth brushing, oral irrigation is an effective alternative to manual tooth brushing and dental floss for reducing bleeding, gingival inflammation, and plaque removal.

Adult↗

PubMed2004

Pulp responses to precise thermal stimuli in dentin-sensitive teeth.

The purpose of this study was to determine whether pulpal responses to cold temperatures applied to enamel, using a method that precisely controls the intensity of the cold stimulus or measures the response time, could distinguish dentin-sensitive teeth from nonsensitive teeth. Eighteen human subjects were stimulated with cold temperatures decreasing in 5 degree C intervals (and with tetrafluoroethane) on exposed root and enamel of a dentin-sensitive tooth and enamel of a contralateral nonsensitive tooth. Pain threshold, intensity of pain, time to pain onset, and duration of pain at baseline, 4 h, 8 h, and 1 week were measured. Responses to enamel stimulation of sensitive teeth compared with the nonsensitive teeth usually were highly correlated and not significantly different. The exception was a longer duration of pain in the dentin-sensitive teeth (4.62 +/- 0.47 s) compared with nonsensitive teeth (2.92 +/- 0.49 s; p = 0.016) after enamel stimulation with tetrafluoroethane. Longitudinal studies are necessary to determine whether these slight increases in pain duration indicate an increased probability of pulpal degeneration or need for dentin protection.

Cold Temperature↗

PubMed2004

Local biochemical markers of bone turnover: relationship to subsequent density of healing alveolar bone defects.

OBJECTIVES: This pilot study was designed to test whether biochemical markers of bone turnover in washes of periosteal or trabecular alveolar bone surfaces could be correlated with increases in bone density of an adjacent healing implant socket. METHODS: Ten subjects had a canula inserted into the alveolar crest and sterile phosphate-buffered saline was washed over the periosteal and trabecular surfaces and collected. Surgical flaps were reflected, 5 mm diameter bone cores were removed from the bone wash site, and standardized radiographs were taken. The sites were allowed to heal for 12 weeks, and radiographs were repeated. Bone washes of the healing sites were also collected after 2 and 12 weeks. Washes were analysed for bone turnover markers osteocalcin (OC; radioimmunoassay) and C-terminal telopeptide of Type 1 collagen (ICTP; enzyme-linked immunosorbent assay (ELISA)), and blood component albumin (ALB; ELISA). Changes in bone density during healing were determined by radiographic absorptiometry. RESULTS: OC/ALB and ICTP/ALB ratios were higher for trabecular than periosteal washes at baseline (p<or=0.01). Trabecular OC/ALB and ICTP/ALB were inversely correlated with increasing bone density of the healing bone core socket (r=-0.72, p=0.03; Pearson's correlation coefficient). CONCLUSIONS: Biochemical markers of bone turnover in bone washes of specific alveolar bone sites may prove helpful in predicting how the bone density will increase around healing dental implants.

Absorptiometry, Photon↗

PubMed2003

Impact of increased occlusal contact, interleukin-1 genotype, and periodontitis severity on gingival crevicular fluid IL-1beta levels.

BACKGROUND: The study of occlusal therapy in humans with periodontitis is problematic due to potential irreversible bone loss in control subjects. The hypothesis of this pilot investigation was that increased interocclusal contact initiated by short-term occlusal splint disuse would increase tooth mobility and the bone-resorptive cytokine interleukin (IL)-1beta in gingival crevicular fluid (GCF), comparable to IL-1-positive genotype and increased periodontitis severity. METHODS: Nineteen non-smoking chronic periodontitis patients using nocturnal occlusal splints and undergoing periodontal maintenance in a private practice were evaluated at five time points: 24 hours after continuous splint use; 1, 2, and 3 days after no occlusal splint use; and 14 days after resumption of customary nighttime splint use. Subjects were evaluated to confirm that the plaque index and gingival index were < or = 1.0, and to categorize past periodontitis (moderate or severe) and IL-1 genotype (1A +4845 plus IL-1B +3954). Test sites on two anterior teeth vulnerable to occlusal trauma were sampled for mobility, GCF IL-1beta, and IL-1 receptor antagonist (ra). RESULTS: Tooth mobility remained low during the 3-day period when patients were not wearing their occlusal appliance. GCF IL-1beta decreased after not wearing the appliances (P = 0.016), especially at 48 hours. At this time, genotype-positive subjects had higher levels of GCF IL-1beta/IL-1ra than genotype-negative subjects (P = 0.045), and patients who had experienced severe periodontitis had higher IL-1beta levels than moderate periodontitis subjects (P = 0.004). CONCLUSIONS: These findings suggest that short-term discontinuation of occlusal splint therapy in non-smoking periodontitis patients undergoing periodontal maintenance does not result in potential signs of early occlusal trauma (increasing mobility or GCF IL-1beta). Longer-term studies may be needed to determine appropriate therapy applications for periodontitis-susceptible patients with definable occlusal discrepancies and/or parafunction.

Adult↗

PubMed2003

Topically applied minocycline microspheres: why it works.

This article presents the results of a single-arm, open-label, multicenter clinical trial of the topical use of sustained-release minocycline hydrochloride (HCl) microspheres as an adjunct to scaling and root planing. The objective of this study was to evaluate the long-term safety and efficacy of the subgingival application of resorbable minocycline microspheres as an adjunct to scaling and root planing in the treatment of chronic periodontitis. The primary outcome measures were the reduction in probing pocket depth at 9- and 12-month evaluations, and the percent of bleeding upon probing. A total of 173 patients with moderate-to-severe chronic periodontitis were enrolled in this multicenter clinical trial. All patients received full-mouth scaling and root planing plus minocycline microspheres in all periodontal pockets that probed > or = 5 mm. All sites treated at baseline and any new sites > or = 5 mm again received minocycline microspheres at 3- and 6-month follow-up appointments with no further scaling and root planing. Significant improvements in all clinical parameters measured were found at all time points (1, 3, 6, 9 and 12 months). The product was found to be well-tolerated by patients, safe, and easy to deliver. Scaling and root planing with the topical application of minocycline microspheres appeared to give better results than would have been expected with scaling and root planing alone.

Absorbable Implants↗

PubMed2003

A comparison of a waterpik dual-motor powered toothbrush and a manual toothbrush in affecting interproximal bleeding reduction and dental biofilm accumulation.

OBJECTIVE: This single-blind, 21-day clinical study was designed to compare the effectiveness of a dual-motor powered toothbrush (SynchroSonic) and a manual toothbrush in affecting interproximal bleeding reduction and dental biofilm accumulation in a cohort of 70 subjects. METHODOLOGY: After baseline evaluations of soft tissue trauma, dental biofilm and interproximal bleeding, subjects were randomly assigned to one of the two experimental groups, given toothbrushing instructions and had their teeth cleaned. At 21 days, the clinical parameters were again evaluated. RESULTS: In the powered toothbrush group, there were 37 subjects at baseline and 36 subjects at follow-up. In the manual toothbrush group, there were 34 subjects at baseline and 33 subjects at follow-up. In the powered toothbrush group, the mean biofilm index fell from 3.46 to 3.12; a 9.7% reduction. In the manual toothbrush group, the mean biofilm index fell from 3.51 to 3.30; a 5.4% reduction. The powered toothbrush group showed significantly greater biofilm reduction (9.7% vs. 5.4%, p = 0.043). In the powered toothbrush group, the mean gingival bleeding index fell from 0.66 to 0.44; a 32% reduction. In the manual toothbrush group, the mean gingival bleeding index fell from 0.66 to 0.53; a 20% reduction. The powered toothbrush group showed significantly greater gingival bleeding reduction (32% vs. 20%, p = 0.02). CONCLUSION: The results demonstrated that both the manual toothbrush and the SynchroSonic powered toothbrush were safe, with no evidence of clinically significant hard or soft tissue abrasion observed. Additionally, the powered toothbrush was more effective in reducing biofilm and gingival bleeding than the manual toothbrush.

Adult↗

PubMed2002

Effect of narcotic pain reliever on pulp tests in women.

The purpose of this study was to determine the effect of one dose of a common narcotic-based pain reliever (Vicodin) on a battery of oral sensitivity tests across time in women. Fifteen Caucasian women randomly were given an oral dose of 10 mg of hydrocodone/1000 mg of acetaminophen or placebo in a double-blind, cross-over design. At baseline (before drug) and after 2, 4, and 8 h each subject was evaluated for sensitivity thresholds with four tests around an experimental tooth: (a) electric pulp tester applied to exposed root; (b) electric pulp tester on adjacent mucosa; (c) increasing probe pressure (grams) on adjacent mucosa; and (d) decreasing cold probe (degrees C) on the exposed root. The outcomes of all tests were not statistically different between drug and placebo treatments at any time point (p > 0.05). These results suggest that a systemic dose of hydrocodone/acetaminophen has little impact on healthy pulp or mucosa sensitivity in women as measured by common diagnostic tests.

Acetaminophen↗

PubMed2002

Effects of simvastatin gels on murine calvarial bone.

BACKGROUND: The cholesterol-lowering drug simvastatin has been shown to stimulate murine calvarial bone growth after multiple injections. The purpose of this study was to test if similar bone stimulation could be induced by 2 single-dose drug delivery systems appropriate to periodontal therapy. METHODS: ICR Swiss mice were treated with the following protocols: 1) injection of methylcellulose gel alone, subcutaneously over the calvarium (INJ-GEL; n = 8); 2) injection of gel with simvastatin (INJ-SIM; 2.2 mg, n = 16); 3) polylactide membrane (PLA) containing gel alone implanted over calvarium (MEM-GEL; n = 10); 4) implanted PLA membrane containing gel and simvastatin (MEM-SIM; n = 10); and 5) untreated mice (n = 12). Animals were sacrificed after 22 or 44 days, calvaria decalcified and stained with hematoxylin and eosin, and images digitized and measured for bone thickness and area. Data were compared using analysis of variance. RESULTS: INJ-SIM stimulated a 53% (P = 0.02) increase at the thickest point of calvarial bone, while MEM-SIM caused a highly significant (P < or = 0.0005) increase in bone thickness (159% to 172%) and bone area (144% to 180%) compared to gel controls. Simvastatin gels caused soft tissue inflammation, which appeared to be related to bone increases. If INJ-SIM animals showing leakage of gel and/or no inflammation were excluded from analysis, INJ-SIM resulted in more bone (58% to 83%) than gel controls. An insignificant amount of SIM-stimulated bone was lost over the long term (44 days). CONCLUSIONS: A single, high dose of simvastatin gel can stimulate murine cranial bone apposition, particularly when delivered under an occlusive membrane. Both approaches should be investigated further for possible development for periodontal therapy.

Analysis of Variance↗

PubMed2002

Comparison of conventional periodontal maintenance versus scaling and root planing with subgingival minocycline.

BACKGROUND: Alternative regimens using subgingival antimicrobials compared to conventional periodontal maintenance (PM) may lead to more efficient protocols. The purpose of this study was to evaluate treatment time and clinical and radiographic outcomes in 2 periodontitis cohorts, one receiving conventional PM and the other receiving scaling and root planing (SRP) and multiple doses of subgingival minocycline. METHODS: Moderate to advanced chronic periodontitis patients were concurrently treated with either: 1) scaling and root planing and 4 subgingival doses of minocycline microspheres in all > or = 5 mm pockets over a 6-month period (RP/M; n = 24 patients); or 2) conventional 3-month periodontal maintenance (PM; n = 24 patients). Clinical and radiographic measurements, including probing depth (PD), clinical attachment level (CAL), and interproximal bone height (BH), were analyzed in 2 premolar/molar interproximal > or = 5 mm pockets at baseline and 1 year using paired t tests, analysis of variance, chi-square analysis, and correlation coefficients. RESULTS: Baseline clinical and radiographic data were similar between RP/M and PM patients. Probing depths showed greater mean improvement in RP/M (0.9 +/- 0.1 versus 0.4 +/- 0.1 mm, P = 0.02), with 25% of subjects in RP/M gaining > or = 2 mm compared to 4.2% in PM (differences were statistically significant). The mean loss in bone height and percent subjects losing bone height were less in RP/M (0.05 +/- 0.05 mm; 12.5%) than PM (0.09 +/- 0.08 mm; 16.7%), but bone height differences were not statistically significant. A subset of RP/M molar furcation sites responded with similar PD reduction and no BH loss over 1 year. While cross-sectional RP/M data between CAL and BH, or PD and CAL were highly correlated, changes over 1 year were not correlated among any of these parameters. CONCLUSIONS: Scaling and root planing and subgingival minocycline in experimental sites took little time (<5 minutes/appointment), but resulted in more probing depth reduction and less frequent bone height loss than conventional periodontal maintenance.

Administration, Topical↗