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Biomedical subjects

R Niederman

Publications and source records attributed to R Niederman.

At least 19 recordsLinked to original sources

A systematic review of in vivo retrograde obturation materials.

PURPOSE: The aim of this study was to answer the question: For patients requiring apicoectomy (apicectomy/root-end resection) and retrograde (root-end) obturation (filling), which retrograde obturation (root-end filling) material(s) is/are the most effective, as determined by reduction in periapical radiolucency and elimination of signs and symptoms? MATERIALS AND METHODS: A MEDLINE and a Cochrane search (two specified searches) were conducted to identify randomised (RCT) and nonrandomised controlled clinical trials (CCT), cohort studies (CS) and case-control studies (CCS), published between 1966 and 2002, October week 4, conducted on humans, and published in English, German and French language, relating to retrograde obturation materials following apicoectomy. RESULTS: The MEDLINE and the Cochrane search identified 324 and 21 published articles, respectively. The Cochrane search identified three additional articles to the MEDLINE-search articles. Fourteen studies met the inclusion criteria: two were RCTs, six were CCTs, none was a CS and six were retrospective CCSs. Nine of the 14 studies compared a new retrograde (root-end)-filling material to amalgam, 4 of the 14 studies compared orthograde root canal fillings to retrograde (root-end) amalgam and the fourteenth study compared variations of a resin composite (Retroplast) when used in combination with the bonding agent Gluma (Bayer AG, Gluma 1 and 2). The two RCTs indicated that glass ionomer cement appeared to be equivalent to amalgam. The six CCTs indicated that orthograde filling with gutta-percha and sealer was more effective than amalgam retrograde (root-end)-filling (one trial). Similarly, retrograde (root-end)-filling with (i) composite and Gluma (Bayer AG, Leverkusen, Germany) as bonding agent (one trial), (ii) reinforced zinc oxide eugenol cement (EBA cement) (Stailine, Staident, Middlesex, England; one trial) and (iii) gold leaf (one trial) appeared to be better than amalgam retrograde (root-end)-filling. Finally, gutta-percha retrograde (root-end)-filling appears to be less effective than amalgam (one trial) and Retroplast with ytterbium trifluoride is better than Retroplast with silver, when they are both used with Gluma as bonding agent (one trial). CONCLUSIONS: For the highest level of evidence (RCT) retrograde (root-end)-filling with glass ionomer cement is almost as effective as amalgam. However, there was a significant caveat as there were only two RCTs. At the next highest level of evidence (CCT), and given the additional caveat that there was only one controlled trial for each material, retrograde (root-end) EBA cement, composite with Gluma and gold leaf, as well as orthograde gutta-percha, may be more effective than retrograde (root-end) amalgam filling. In conclusion, these results suggest that additional validating CCTs and RCTs are needed.

Apicoectomy↗

Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice.

BACKGROUND: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. METHODS: We tested this hypothesis prospectively using P/E-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. RESULTS: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a 10-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. CONCLUSIONS: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships.

Alveolar Bone Loss↗

Benchmarking the endodontic literature on MEDLINE.

The purpose of this study was to identify and quantify the endodontic literature available for clinical decision making. A search strategy based on Medical Subject Headings for endodontics was developed to examine MEDLINE. The identified articles were limited to human subjects and English. Sensitive and specific methodological search filters identified four categories of information: etiology, diagnosis, therapy, and prognosis. The results were then subdivided by year to identify trends. Between 1990 and 1998 MEDLINE identified 3,152 articles published in English on endodontics in humans. The number of articles per year (mean +/- SD) for sensitive and specific searches was etiology (28+/-10, 1+/-2), diagnosis (38+/-11, 1+/-1), therapy (59+/-15, 3+/-3), and prognosis (40+/-13, 10+/-5), respectively. The number of articles in each category increased by 1 to 3% each year. There were 150 articles/yr in endodontics in at least 120 journals cited on MEDLINE on which to base clinical decisions.

Analysis of Variance↗

Variation, certainty, evidence, and change in dental education: employing evidence-based dentistry in dental education.

Variation in health care, and more particularly in dental care, was recently chronicled in a Readers Digest investigative report. The conclusions of this report are consistent with sound scientific studies conducted in various areas of health care, including dental care, which demonstrate substantial variation in the care provided to patients. This variation in care parallels the certainty with which clinicians and faculty members often articulate strongly held, but very different opinions. Using a case-based dental scenario, we present systematic evidence-based methods for accessing dental health care information, evaluating this information for validity and importance, and using this information to make informed curricular and clinical decisions. We also discuss barriers inhibiting these systematic approaches to evidence-based clinical decision making and methods for effectively promoting behavior change in health care professionals.

Attitude of Health Personnel↗

Effectiveness of dentist-prescribed, home-applied tooth whitening. A meta analysis.

INTRODUCTION: Common clinical experience suggests that tooth whitening agents are 100% effective. This study uses meta-analysis of data from published randomized controlled clinical trials to determine the efficacy of tooth whitening agents. METHODS: A MEDLINE search strategy was developed and implemented to systematically identify clinical trials on dentist-prescribed, home-applied tooth whitening agents, using 10% carbamide peroxide, published between 1989-1999. Inclusion criteria (e.g., in English, human clinical trials) and exclusion criteria (e.g., not placebo controlled) were established and clinical trials that met these criteria were critically appraised for validity and clinical applicability. Meta-analysis was then used to quantitatively integrate the findings. RESULTS: Seven studies were identified that met the inclusion and validity criteria. These studies indicated that: Whitening results in a significant mean change of 6 4 shade guide units (p < 0.01), while the placebo control group exhibited little change (0.7 0.6, p > 0.05). 93% of the bleached patients exhibited 2 shade guide unit change, while 20% of the placebo control group exhibited this change. The brand of bleaching agent had a significant effect on tooth whitening, but the daily application time and duration of treatment did not. Whitening is maintained for 6 months for 1/2 of the people treated. Neither gingival indices nor plaque indices were adversely or favorably affected by bleaching. CLINICAL APPLICABILITY: The data from the reviewed studies indicate that rather than being 100% effective, on average: 73% (93% for bleached group minus 20% placebo group) of people who whiten their teeth will exhibit a whitening that is 2 shade guide units greater than the placebo. 20% of the people who use dentist-prescribed, home-applied bleaching will achieve a mean whitening effect of 5 shade guide units. Re-treatment for 50% of people may be necessary to maintain this effect longer than 6 months. The methods used here are Internet applicable for other clinical topics.

Adult↗

Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice.

Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E-/- selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E-/- mice and P/E+/+ wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periapical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1alpha. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases were not statistically significant. Only IL-12 was higher in P/E+/+ mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction.

Animals↗

Improving quality of life for people with chronic conditions: the example of t'ai chi and multiple sclerosis.

CONTEXT: The greatest needs of people with chronic conditions are long-term care, maximized independence, and improved quality of life. With conventional medicine becoming increasingly expensive, depersonalized, and unable to adequately meet such needs, many with chronic conditions are seeking health promotion strategies to effectively manage their symptoms. OBJECTIVE: An 8-week t'ai chi program was conducted to explore psychosocial and physical benefits for those with multiple sclerosis. DESIGN: Nonrandomized, noncontrolled pilot study. SETTING: American College of Traditional Chinese Medicine, San Francisco, Calif. PATIENTS: 19 patients with multiple sclerosis. INTERVENTION: T'ai chi. MAIN OUTCOME MEASURES: Walking speed (distance = 25 ft), hamstring flexibility, and psychosocial well-being as measured by the Medical Outcomes Study 36-item Short-form Health Survey. RESULTS: Walking speed increased by 21% and hamstring flexibility increased by 28%. Patients experienced improvements in vitality, social functioning, mental health, and ability to carry out physical and emotional roles. CONCLUSIONS: This pilot program was conducted entirely on a volunteer basis and led to the implementation of several additional t'ai chi classes for people with multiple sclerosis across the United States. T'ai chi and other health promotion programs offer help toward achieving the goals of increasing access to services, maximizing independence, and improving quality of life for people with chronic disabling conditions.

Chronic Disease↗

Propionic acid stimulates superoxide generation in human neutrophils.

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate (IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3 formation and Ca2+ mobilization but also superoxide generation. The IP3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca2+]i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca2+]i, which was higher than the basal level, following a transient increase in [Ca2+]i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+ ionophore and a Ca2+ influx activator.

Adult↗

Short chain carboxylic acids decrease human gingival keratinocyte proliferation and increase apoptosis and necrosis.

Epithelia are key barriers to infections. In periodontal disease, the gingival sulcular epithelium becomes ulcerated. In this report, we test the hypothesis that short-chain carboxylic acids (SCCA) inhibit keratinocyte proliferation, increase necrosis and apoptosis, and may thus promote ulceration. SCCA produced by bacteria are present at millimolar concentrations in the periodontal pockets of subjects with periodontal disease. SCCA concentrations are higher in subjects with severe disease than in those with mild disease, and are not detectable in healthy subjects. Cell proliferation is critical for maintenance of epithelial barrier function. All SCCA tested, when neutralized, decreased epithelial cell proliferation (as measured by 3H-thymidine incorporation) in a dose-dependent manner. We found that epithelial cell viability decreased with increasing SCCA concentrations, accounting at least partly for the decreased 3H-thymidine incorporation. For all conditions we tested, SCCA-induced apoptosis preceded and exceeded necrosis. While the molecular mechanism(s) for these effects remain to be determined, the results indicate that SCCA derived from caries- or periodontal disease-associated bacteria could alter gingival barrier function.

Apoptosis↗

Evidence-based esthetic dentistry.

Evidence-based clinical practice integrates the best available evidence with clinical expertise. This article presents a clinical case scenario and, using a four-step, evidence-based approach, demonstrates how to (1) ask an evidence-based question; (2) search MEDLINE for the best evidence; (3) critically appraise the evidence; and (4) apply the evidence to the patient. The procedure is demonstrated with the sample question, Does bleaching of bonded porcelain veneers increase marginal leakage? A MEDLINE search strategy was developed for synonyms of the key words that best identify the problem, the intervention, and the outcome. The synonyms were combined using the Boolean operator "or" to identify a "sensitive" (i.e., inclusive) universe of 140,000 journal articles. These categories were then combined using the Boolean operator "and" to identify the most "specific" (i.e., exclusive) four articles from among the 140,000. Finally, to find the best evidence, the articles were limited to "humans" and "randomized controlled trials." This identified one article. Critical appraisal of the limited data in this one article indicates that the methods are valid and statistically significant, but because of the methods employed, may not be clinically important. Evidence-based methods take one to the edge of the available information universe in about 15 minutes. The results can be both exhilarating and sobering. They can indicate the depth or limits of available information and suggest gaps in the knowledge-base that require further study. Most importantly, however, the results allow practitioners to communicate incisively and truthfully with patients and to make more informed clinical choices.

Aged↗

Gingival inflammation induced by food and short-chain carboxylic acids.

Earlier studies in our laboratories demonstrated that particles of a number of snack foods that are retained on the dentition accumulate fermentable sugars and short-chain carboxylic acids (SCCA; acetic, formic, lactic, and propionic) to different degrees. The present study was undertaken to test the hypothesis that the accumulated SCCA can induce a gingival inflammatory response. Five periodontally and medically healthy subjects were given portions of plain doughnuts (high SCCA levels) or oatmeal cookie (low SCCA), or had the SCCA applied directly to the gingival margins of designated teeth. Subjects were given wax to chew, or nothing, as controls. Inflammation was assessed by measurements of subgingival temperature, flow rates of gingival crevicular fluid (GCF), and neutrophil emigration into GCF. Subgingival temperatures of the maxillary gingiva rose by 1.32 +/- 0.30 degrees C (mean +/- SE) 5 min after the subjects consumed the doughnuts and remained elevated for at least 1 hr. These values were significantly higher than those obtained from subjects after ingestion of oatmeal cookies (0.63 +/- 0.17 degree C; p < 0.01), consistent with the low levels of SCCA in the retained cookie particles. Wax chewing elicited a similar response, indicating a masticatory effect on the gingiva. Gingival temperatures in the unchallenged controls remained unchanged. Neutrophil emigration into the GCF was significantly elevated in subjects after doughnut consumption. Rinses with a solution of SCCA, or application of the SCCA to the gingiva, also brought about significant elevations in subgingival temperature and neutrophil emigration. The findings describe the inflammatory effects of food ingestion on the gingiva of healthy human subjects, and support the hypothesis that SCCA in the particles of retained food are at least partly responsible for the observed responses.

Acetic Acid↗

Short-chain carboxylic acid concentration in human gingival crevicular fluid.

Short-chain carboxylic acids (e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which can accumulate in the gingival crevice. It is of no small consequence, therefore, that 1- to 5-mM concentrations of these acids exhibit significant biological activity, including the ability to alter cell proliferation and gene expression in cells of importance to the periodontium. This communication reports on the in vivo concentrations of propionic and butyric acid in the gingival crevices of periodontal subjects with severe and mild disease. The results indicated that severely diseased subjects exhibited a > 10-fold increase in the mM concentration of these acids when compared with mildly diseased subjects (mean propionic acid-severe = 9.5 +/- 1.8 mM, and mild = 0.8 +/- 0.3 mM; mean butyric acid-severe = 2.6 +/- 0.4 mM, and mild = 0.2 +/- 0.04 mM). These differences (mean +/- SE) were significant (p < 0.0001). The propionic and butyric acid concentrations were below detection limits in healthy sites of mildly diseased subjects. The propionic and butyric acid concentrations also associated significantly with clinical measures of disease severity (e.g., pocket depth, attachment level) and inflammation (e.g., subgingival temperature, % of sites bleeding when probed), and with the total microbial load (all p < 0.05). Taken together, these data suggest that short-chain carboxylic acids play a mediating role in periodontal disease pathogenesis.

Aggregatibacter actinomycetemcomitans↗

Short-chain carboxylic-acid-stimulated, PMN-mediated gingival inflammation.

This communication reviews the effects of short-chain carboxylic acids on human cells of importance to the periodontium. The central hypothesis is that these acids can alter both cell function and gene expression, and thus contribute to the initiation and prolongation of gingival inflammation. Short-chain carboxylic acids [CH3-(CH2)x-COOH, x < 3] are metabolic intermediates with a broad range of apparently paradoxical biological effects. For example, lactic acid (CH3-CHOH-COOH), a 3-carbon alpha-hydroxy-substituted acid, is widely recognized for its cariogenicity. Lactic acid, however, also occurs in tropical fruits, and is the active ingredient in a variety of anti-wrinkle creams developed by dermatologists. In marked contrast, the unsubstituted 3-carbon propionic acid (CH3-CH2-COOH) is used as a food preservative and is the active principle for one class of non-steroidal anti-inflammatory agents. Interestingly, the addition of one carbon to propionic acid dramatically changes the biological effects. The unsubstituted 4-carbon butyric acid (CH3-CH2-CH2-COOH) is used by hematologists as a de-differentiating agent for the treatment of sickle cell anemia, but by oncologists as a differentiating agent for cancer chemotherapy. Finally, acting either individually or in concert, these acids can increase vascular dilation. Clearly, these acids, while metabolically derived, have a number of very divergent activities which are cell-type-specific (Fig. 1). It may be telling that periodontal bacteria produce these acids in millimolar concentrations, and that these bacteria can be characterized by their acid production profiles. It is no less interesting that these acids occur in the gingival crevices of human subjects with severe periodontal disease at millimolar levels which are > 10-fold higher than those found in mildly diseased subjects, and are undetectable in healthy subjects. Further, when applied directly to healthy human gingiva, short-chain carboxylic acids stimulate a gingival inflammatory response and inflammatory cytokine release. At the cellular level, these acids inhibit proliferation of gingival epithelial and endothelial cells, and inhibit leukocyte apoptosis and function, but can stimulate leukocyte cytokine release. At the molecular level, these acids can stimulate neutrophil gene transcription, translation, and protein expression. Thus, the likelihood is high that these acids, in addition to their cariogenic activity, can promote and prolong gingival inflammation. Our challenge will be to identify the cell or cells of the periodontium which respond to short-chain carboxylic acids, to delineate their responses and the molecular mechanism(s) of these effects, and to categorize the aspects of the inflammatory components which damage and those which protect the host. With this information, it may be possible to begin to rationally identify and test pharmaceutical agents which diminish the harmful aspects, while enhancing the beneficial components, of the inflammatory response.

Bacteria, Anaerobic↗

Effectiveness of the Sonicare sonic toothbrush on reduction of plaque, gingivitis, probing pocket depth and subgingival bacteria in adolescent orthodontic patients.

The Sonicare sonic toothbrush and a traditional manual toothbrush were compared for efficacy in improving periodontal health in young orthodontic patients with existing gingival inflammation. A 4-week, single-blind clinical trial was employed. Twenty-four subjects, ages 11-17 years, who were fully bonded and banded with fixed orthodontic appliances were selected. Subjects were randomly assigned to use either the manual or the Sonicare toothbrush, instructed in its use, and asked to brush each morning and evening for 2 minutes. Plaque index, gingival index, percentage of sites which bled on probing, pocket depth, and total gram-negative bacteria in a subgingival plaque sample were assessed at baseline and 4 weeks around the banded teeth. The results demonstrate that the Sonicare brush was significantly more effective than the manual brush in all clinical parameters. Sonicare was statistically superior to the manual brush in supragingival plaque reduction (57% vs. 10%, respectively; p < 0.001). Gingival Index scores fell by 29 percent in the Sonicare group, but only 3 percent in the manual group. Reduction of bleeding on probing was significantly greater in the Sonicare group than in the manual group (p < 0.001). The Sonicare group decreased from 78% bleeding sites at baseline to 24.5% after 1 month. In the manual group there was only a slight reduction in bleeding on probing (70% of sites at baseline and 64.6% sites after 1 month). Mean pocket depths were significantly reduced compared to baseline values in both the Sonicare and the manual groups (p < 0.001). Pocket depth reduction in the Sonicare group was, however, significantly greater than in the manual group (28% vs. 6%, respectively: p < 0.001). Total gram-negative bacteria in subgingival plaque samples from banded test teeth of a subset of patients were reduced in the Sonicare group (p < or = 0.05), but increased in the manual group. These results clearly demonstrate that the Sonicare sonic toothbrush is superior to a manual toothbrush in improving periodontal health in adolescent orthodontic patients with existing gingivitis.

Adolescent↗

The relationship of gingival crevicular fluid short chain carboxylic acid concentration to gingival inflammation.

Short-chain carboxylic acids (SCCA; C < or = 5; e.g., lactic acid, propionic acid, butyric acid) are metabolic by-products of bacterial metabolism which accumulate in the gingival crevice, and exhibit significant biological activity, including the ability to alter gene expression. It has been hypothesized that among the activities of SCCAs are their ability to contribute to gingival inflammation. This concept complements the notion that specific periodontal pathogens are the causative agents of gingival inflammation. To begin testing these 2 hypotheses, we examined the relationship between SCCA concentrations, specific putative periodontal pathogens, and gingival inflammation in medically healthy periodontally diseased subjects. We reasoned that if SCCAs and/or specific periodontal pathogens were causative gingival inflammatory agents, gingival inflammation should increase with increasing concentration of the inflammatory mediator. We also recognized that other clinical variables needed to be controlled for, and an objective quantitative assessment of gingival inflammation used. To accomplish these tasks, sites within subjects were stratified by location and pocket depth, and the following quantified: bacterial presence; SCCA concentration; and gingival inflammation. The results indicated that gingival inflammation directly and significantly correlated with SCCA concentrations in the maxillary and mandibular molars, incisors and canines (all r > or = 0.47; all p < or = 0.015; too few bicuspids were available for complete analysis). The relationship between gingival inflammation and SCCA concentration was best described by a natural log relationship. Gingival inflammation did not, however, correlate positively with either the total number of specific putative periodontal pathogens, or the sum of subsets of these pathogens (-0.31 < or = r < or = 0.39; 0.08 < or = p < or = 0.75) for any of the locations. Finally, the SCCA concentration did not correlate with the level of individual or groups of pathogens. These data, together with historical work and other preliminary data, support the hypothesis that SCCA, rather than specific putative periodontal pathogens, may be a causative agent in gingival inflammation. This work may, in part, begin to explain the apparent lack of a direct relationship between current gingival inflammation and the prediction of bacterially mediated periodontal attachment loss.

Aggregatibacter actinomycetemcomitans↗