Albert Kingman

Periodontal Status in the United States, 1988–91: Prevalence, Extent, and Demographic Variation

This paper reports estimates of the periodontal status of US population derived from data from Phase 1 of the Third National Health and Nutrition Examination Survey conducted by the National Center for Health Statistics in collaboration with the National Institute of Dental Research from 1988 to 1991. A total of 7,447 dentate individuals 13 years of age and older, representing approximately 160.3 million civilian non-institutionalized Americans, received a periodontal assessment. Measurements of gingival bleeding, gingival recession level, periodontal pocket depth, and calculus were made by dental examiners. Assessments were made at the mesiobuccal and mid-buccal sites of all fully erupted permanent teeth present in two randomly selected quadrants, one maxillary and one mandibular. All data were weighted and standard errors calculated by special software to adjust for the effect of sample design. Although over 90% of persons 13 years of age or older had experienced some clinical loss of attachment (LA), only 15% exhibited more severe destruction (LA ≥ 5 mm). Prevalence of moderate and severe LA and gingival recession increased with age, while prevalence of pockets ≥ 4 mm or ≥ 6 mm did not. These data suggest that the increasing prevalence of LA with age is more associated with increasing prevalence of recession than with changes in the prevalence of pockets or age. The extent or number of affected sites with advanced conditions for loss of attachment, pocket depth, or recession was not large for any age group. Differences in prevalence of moderate and severe loss of attachment, moderate and deep pockets, and recession were found among gender and race-ethnicity groups. Females exhibited better periodontal health than males, and non-Hispanic whites exhibited better periodontal health than either non-Hispanic blacks or Mexican-Americans.

In vivo bone formation by human bone marrow stromal cells: Effect of carrier particle size and shape

Successful closure of bone defects in patients remains an active area of basic and clinical research. A novel and promising approach is the transplantation of human bone marrow stromal cells (BMSCs), which have been shown to possess a significant osteogenic potential. The extent and quality of bone formation by transplanted human BMSCs strongly depends on the carrier matrix with which cells are transplanted; to date, hydroxyapatite/tricalcium phosphate (HA/TCP) supports far more osteogenesis than any other matrix tested. In order to further improve the technique of BMSC transplantation, we studied whether commercially available HA/TCP particles, clinically approved as an osteoconductive material and commercially available as particles measuring 0.5-1.0 mm diameter, is an optimum matrix for promoting bone development by BMSCs. HA/TCP and HA particles of varying size were sieved into a variety of size ranges, from <0.044 mm to 1.0-2.0 mm. Transplants were formed by mixing 40 mg aliquots of particles with cultured passaged human BMSCs. They were placed in subcutaneous pockets in immunocompromised Bg-Nu-XID mice and harvested 4 or 10 weeks later. The transplants were examined histologically; the presence of bone within each transplant was evaluated using histomorphometry or blindly scored on a semiquantitative scale. Transplant morphology and the amount of new bone varied in a consistent fashion based on particle size and shape. Transplants incorporating HA/TCP particles of 0.1-0.25 mm size demonstrated the greatest bone formation at both 4 and 10 weeks; larger or smaller particles were associated with less extensive bone formation, while a size of 0.044 mm represented a threshold below which no bone formation could be observed. Flat-sided HA particles measuring 0.1-0.25 mm formed no bone. The differences in bone formation were not attributable to the differences in cell attachment among the groups. Instead, the size and spatial and structural organization of the particles within BMSC transplants appear to determine the extent of bone formation. These findings provide necessary information for the successful clinical application of BMSC transplantation techniques.

Coronal and root caries in the dentition of adults in the United States, 1988-1991.

Dental public health policy planning requires accurate and current information about the extent of caries in the United States population. These data are available from the caries examination from Phase 1 of the Third National Health and Nutrition Examination Survey, which found that 94% of adults in the United States show evidence of past or present coronal caries. Among the dentate, the mean number of decayed and filled coronal surfaces per person was 21.5. Dentate females had a lower number of untreated coronal tooth surfaces with caries (1.5), but a higher mean number of treated and untreated surfaces per person (22.7) than males, with scores of 2.1 and 20.2, respectively. Estimates for race-ethnicity groups were standardized by age and gender to control for population differences among them. Dentate non-Hispanic blacks (11.9) and Mexican-Americans (14.1) had half the number of decayed and filled coronal surfaces as non-Hispanic whites (24.3), but more untreated surfaces (non-Hispanic whites, 1.5; non-Hispanic blacks, 3.4; Mexican-Americans, 2.8). Mexican-Americans were most likely to be dentate, had the highest average number of teeth, and had 25% fewer decayed, missing, and filled coronal surfaces (37.6) than non-Hispanic blacks (49.2) and non-Hispanic whites (51.0). Root caries affected 22.5% of the dentate population. Blacks had the most treated and untreated root surfaces with caries (1.6), close to the value for Mexican-Americans (1.4). The score for non-Hispanic whites was 1.1. Untreated root caries is most common in dentate non-Hispanic blacks (1.5), followed by Mexican-Americans (1.2), with non-Hispanic whites (0.6) having the fewest untreated carious root surfaces. Race-ethnicity groups were disparate with respect to dental caries; effort is needed to treat active caries common in some population subgroups.

Transdermal clonidine compared to placebo in painful diabetic neuropathy using a two-stage 'enriched enrollment' design.

&NA; Because a variety of mechanisms may generate pain in neuropathic pain syndromes, conventional clinical trial methods may fail to identify some potentially useful drugs; a drug affecting just a single mechanism may work in too few patients to yield a statistically significant result for the trial. To test a previous clinical observation that approximately one‐quarter of patients with painful diabetic neuropathy appear responsive to clonidine, we conducted a formal clinical trial of transdermal clonidine in painful diabetic neuropathy patients using a 2‐stage enriched enrollment design. In the first stage (study I), 41 patients with painful diabetic neuropathy completed a randomized, 3‐period crossover comparison of transdermal clonidine (titrated from 0.1 to 0.3 mg/day) to placebo patches. Twelve apparent responders from study I were entered into the ‘enriched enrollment’ second stage (study II), consisting of an additional 4 double‐blind, randomized, 1‐week treatment periods with transdermal clonidine and placebo. Study I showed that in the overall group of 41 patients, pain intensity differed little during clonidine and placebo treatment. In study II, however, the 12 apparent responders from study I had 20% less pain with clonidine than placebo (95% confidence interval (CI): 4–35% pain reduction; P = 0.015), confirming that their pain was responsive to clonidine. None of the 3 consistent clonidine responders who were tested with the &agr;‐adrenergic blocker phentolamine had relief of pain, suggesting that clonidines pain relief is not mediated by a decrease in sympathetic outflow. A post‐hoc analysis of many variables suggested that patients who described their pain as sharp and shooting may have a greater likelihood of responding to clonidine. The results of this study support the hypothesis that there is a subset of patients with painful diabetic neuropathy who benefit from systemic clonidine administration and illustrate the value of an enriched enrollment technique in analgesic trials.

Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study

BACKGROUND Adult bone marrow-derived (BMD) cells could be used to repair damaged organs and tissues, but the intrinsic plasticity of these cells has been questioned by results of in-vitro studies suggesting that such cells might fuse with other cells giving the appearance of differentiation. We aimed to determine whether fusion events are important in vivo. METHODS To test whether BMD cells can colonise an epithelial tissue and differentiate there without fusion, we did in-situ hybridisation with Y and X chromosome probes labelled with 35-sulphur or digoxigenin, or labelled fluorescently. We did immunohistochemistry with anticytokeratin 13 along with fluorescence in-situ hybridisation to identify Y-chromosome positive buccal epithelial cells in cheek scrapings obtained from five females who had received either a bone-marrow transplant or an allogeneic mobilised peripheral-blood progenitor-cell transplant (enriched in CD34+ cells) from male donors. FINDINGS When examined 4-6 years after male-to-female marrow-cell transplantation, all female recipients had Y-chromosome-positive buccal cells (0.8-12.7%). In more than 9700 cells studied, we detected only one XXXY-positive cell (0.01%) and one XXY cell (0.01%), both of which could have arisen when an XY cell fused with an XX cell. INTERPRETATION Male BMD cells migrate into the cheek and differentiate into epithelial cells, an occurrence that does not depend on fusion of BMD cells to recipient cells. This finding might be an example of transdifferentiation of haemopoietic or stromal progenitor cells. Plasticity of BMD cells could be useful in regenerative medicine.

Mercury Concentrations in Urine and Whole Blood Associated with Amalgam Exposure in a US Military Population

Minute amounts of mercury vapor are released from dental amalgams. Since mercury vapor is known to be associated with adverse health effects from occupationally exposed persons, questions regarding the margin of safety for exposure to mercury vapor in the general population continue to be raised. To address this issue, one needs information regarding exposure to mercury vapor from dental amalgam fillings and its possible consequences for health in the general population. The NIDR Amalgam Study is designed to obtain precise information on amalgam exposure and health outcomes for a non-occupationally-exposed population of US adults. One hypothesis was that in a generally healthy population a significant association between amalgam exposure and Hg levels in urine and/or whole blood could be detected. The cohort investigated was an adult military population of 1127 healthy males. Their average age was 52.8 years, and their ages varied from 40 to 78 years. Ninety-five percent of the study participants were white males, and slightly over 50% had some college education. Five percent were edentulous. The dentate participants, on average, had 25 natural teeth, 36.9 decayed or filled surfaces (DFS), and 19.9 surfaces exposed to amalgam, with amalgam exposure varying from 0 to 66 surfaces. Their average total and inorganic urinary mercury concentrations were 3.09 μg/L and 2.88 pg/L. The average whole-blood total and inorganic mercury concentrations were 2.55 ug/L and 0.54 μg/L. Significant correlations were detected between amalgam exposure and the total (r = 0.34, p < 0.001) and inorganic 0.34 (r = 0.34, p < 0.001) urinary mercury concentrations on the original scale. Stronger correlations were found for total (r = 0.44, p < 0.001) and inorganic (r = 0.41, p < 0.001) urinary Hg on the log scale, as well as for creatinine-corrected total (r = 0.43, p < 0.001) and inorganic (r = 0.43, p < 0.001) urine concentrations. In whole blood, statistically significant, but biologically weak, correlations were detected for total (r = 0.09, p = 0.005) and inorganic (r = 0.15, p < 0.001) Hg concentrations, respectively. Based on these cross-sectional data, it is estimated that, on average, each ten-surface increase in amalgam exposure is associated with an increase of 1 ug/L mercury in urine concentration.

Candidate Gene Studies of Human Pain Mechanisms Methods for Optimizing Choice of Polymorphisms and Sample Size

,coronary stenosis, rheumatoid arthritis, or lumbar discherniation—clinical pain researchers have made littleuse of these genomic riches to study variations in painprocessing, given a uniform initiating injury. The plausi-bility of clinical pain genetic studies is supported by therecent findings of major differences between inbredmouse strains in the behavioral response to more than20 different acute and chronic pain conditions, includingthermal and chemical stimulation of the skin and visceraand nerve injury.

Effect of partial recording protocols on severity estimates of periodontal disease

OBJECTIVES The study aim was to assess bias magnitudes of periodontal disease severity estimates for specific partial recording protocols (PRPs) in epidemiological studies. MATERIAL AND METHODS Estimates of mean clinical attachment loss (MCAL) and mean probing pocket depth (MPPD) were derived for 20 different PRPs using full-mouth periodontal data from 1437 dentate Brazilian subjects 14-103 years old having at least four teeth. Biases, relative biases and intra-class correlations for all PRPs were evaluated. Graphical methods were used to assess how well the PRP-based estimates agreed with full-mouth scores across levels of disease. RESULTS Slightly higher levels of disease were evidenced on lingual than on buccal sites. Seven multi-site PRPs and the Ramfjörd PRP produced small biases in MPPD (-0.17 to 0.04 mm) and MCAL with relative biases under 8% and 4% in absolute value for MPPD and MCAL, respectively. Biases for full- and random half-mouth-based PRPs were similar. The three-site random half-mouth MB-B-DL and the Ramfjörd PRPs produced the smallest biases, with relative biases <3% in absolute value for MPPD and MCAL. CONCLUSIONS Bias for MPPD or MCAL estimates varies by site type, number of sites per tooth and number of quadrants included in the PRP.

Comparison of Tooth Surface-specific Dental Caries Attack Patterns in US Schoolchildren from Two National Surveys

The 1979-1980 and the 1986-1987 National Institute of Dental Research (NIDR) surveys of school-aged children revealed that virtually all tooth surfaces experienced a decrease in caries prevalence during the inter-survey period. Overall, there was a 28% decrease in the proportion of tooth surfaces attacked by caries for the primary dentition between the two surveys. The decrease for primary incisors was numerically small (5 surfaces per thousand surfaces at risk) and not statistically significant, whereas decreases in the canines and primary molars were considerably larger (23 surfaces per thousand) and statistically significant. For the permanent dentition, the overall decrease in the proportion of surfaces attacked was 35% during the 1979-87 period. Differences between the two surveys in the proportions of surfaces with caries were largest for pit and fissure surfaces (56 surfaces per thousand), followed by those for posterior approximal surfaces (14 surfacesper thousand) and all other smooth surfaces (5 surfaces per thousand). Almost all of these differences were statistically significant, except for some surfaces which experienced very few caries.

A clinical genetic method to identify mechanisms by which pain causes depression and anxiety

BackgroundPain patients are often depressed and anxious, and benefit less from psychotropic drugs than pain-free patients. We hypothesize that this partial resistance is due to the unique neurochemical contribution to mood by afferent pain projections through the spino-parabrachial-hypothalamic-amygdalar systems and their projections to other mood-mediating systems. New psychotropic drugs for pain patients might target molecules in such brain systems. We propose a method to prioritize molecular targets by studying polymorphic genes in cohorts of patients undergoing surgical procedures associated with a variable pain relief response. We seek molecules that show a significant statistical interaction between (1) the amount of surgical pain relief, and (2) the alleles of the gene, on depression and anxiety during the first postoperative year.ResultsWe collected DNA from 280 patients with sciatica due to a lumbar disc herniation, 162 treated surgically and 118 non-surgically, who had been followed for 10 years in the Maine Lumbar Spine Study, a large, prospective, observational study. In patients whose pain was reduced >25% by surgery, symptoms of depression and anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the first postoperative measurement. In patients with little or no surgical pain reduction, mood scores stayed about the same on average. There was large inter-individual variability at each level of residual pain. Polymorphisms in three pre-specified pain-mood candidate genes, catechol-O-methyl transferase (COMT), serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not associated with late postoperative mood or with a pain-gene interaction on mood. Although the sample size did not provide enough power to persuasively search through a larger number of genes, an exploratory survey of 25 other genes provides illustrations of pain-gene interactions on postoperative mood – the mu opioid receptor for short-term effects of acute sciatica on mood, and the galanin-2 receptor for effects of unrelieved post-discectomy pain on mood one year after surgery.ConclusionGenomic analysis of longitudinal studies of pain, depression, and anxiety in patients undergoing pain-relieving surgery may help to identify molecules through which pain alters mood. Detection of alleles with modest-sized effects will require larger cohorts.