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Albert Kingman

Publications and source records attributed to Albert Kingman.

12 recordsLinked to original sources

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

BACKGROUND: Pain 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. RESULTS: We 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. CONCLUSION: Genomic 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.

Anxiety Disorders↗

Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model.

PURPOSE: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. EXPERIMENTAL DESIGN: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. RESULTS: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (approximately 50-60%). I.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. CONCLUSIONS: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers.

Animals↗

Surveillance for dental caries, dental sealants, tooth retention, edentulism, and enamel fluorosis--United States, 1988-1994 and 1999-2002.

PROBLEM/CONDITION: Dental caries is a common chronic disease that causes pain and disability across all age groups. If left untreated, dental caries can lead to pain and infection, tooth loss, and edentulism (total tooth loss). Dental sealants are effective in preventing dental caries in the occlusal (chewing) and other pitted and fissured surfaces of the teeth. Enamel fluorosis is a hypomineralization of enamel related to fluoride exposure during tooth formation (first 6 years for most permanent teeth). Exposure to fluoride throughout life is effective in preventing dental caries. This is the first CDC Surveillance Summary that addresses these conditions and practices. REPORTING PERIOD: 1988-1994 and 1999-2002. SYSTEM DESCRIPTION: The National Health and Nutrition Examination Survey (NHANES) is an ongoing survey of representative samples of the civilian, noninstitutionalized U.S. population aged >/=2 months in NHANES 1988-1994 and all ages during 1999-2002. The dental component gathered information on persons aged >/=2 years. RESULTS: During 1999-2002, among children aged 2-11 years, 41% had dental caries in their primary teeth. Forty-two percent of children and adolescents aged 6-19 years and approximately 90% of adults had dental caries in their permanent teeth. Among children aged 6-19 years, 32% had received dental sealants. Adults aged >/=20 years retained a mean of 24 of 28 natural teeth and 8% were edentulous. Among persons aged 6-39 years, 23% had very mild or greater enamel fluorosis. Disparities were noticed across all age groups, among racial/ethnic groups, persons with lower education and income, and by smoking status. From 1988-1994 to 1999-2002, four trends were observed: 1) no change in the prevalence of dental caries in primary teeth among children aged 2-11 years, 2) a reduction in prevalence of caries in permanent teeth of up to 10 percentage points among persons aged 6-19 years and up to six percentage points among dentate adults aged >/=20 years, 3) an increase of 13 percentage points in dental sealants among persons aged 6-19 years, and 4) a six percentage point reduction in total tooth loss (edentulism) among persons aged >/=60 years. INTERPRETATION: The findings of this report indicate that the dental caries status of permanent teeth has improved since the 1988-1994 survey. Despite the decrease in caries prevalence and severity in the permanent dentition and the increase in the proportion of children and adolescents who benefit from dental sealants, disparities remain. PUBLIC HEALTH ACTION: These data provide information for public health professionals in designing interventions to improve oral health and to reduce disparities in oral health, for researchers in assessing factors associated with disparities and dental caries in primary teeth, and in designing timely surveillance tools to monitor total fluoride exposure.

Adolescent↗

Amalgam exposure and neurological function.

Concerns regarding the safety of silver-mercury amalgam fillings continue to be raised in the absence of any direct evidence of harm. The widespread population exposure to amalgam mandated that a thorough investigation be conducted of its potential effects on the nervous system. The National Institute of Dental and Craniofacial Research and U.S. Air Force investigators collaborated in the ongoing Air Force Health Study (AFHS) of Vietnam era veterans. The primary study question involved adverse health effects associated with exposure to herbicides or dioxin. An assessment of exposure to dental amalgam fillings was added to the 1997-1998 health examination to investigate possible associations between amalgam exposure and neurological abnormalities. Our study population consisted of 1663 dentate AFHS participants, comprised of 986 AFHS controls and 677 Ranch Hand veterans who were exposed to dioxin in Vietnam. Two hundred and fifty-two of the participants had confirmed diabetes mellitus. Study outcomes included clinical neurological signs, vibrotactile thresholds, and summary variables for different levels of peripheral neuropathy. A limitation of our study is that our database did not include more sensitive continuous measures such as nerve conduction studies. No significant associations were found between amalgam exposure and clinical neurological signs of abnormal tremor, coordination, station or gait, strength, sensation, or muscle stretch reflexes or for any level of peripheral neuropathy among our study participants. A statistically significant association was detected between amalgam exposure and the continuous vibrotactile sensation response for the combined non-diabetic participants and separately for non-diabetic AFHS controls. No significant association in this measure was detectable for non-diabetic Ranch Hand veterans or among the combined diabetic participants. The association is a sub-clinical finding that was not associated with symptoms, clinically evident signs of neuropathy, or any functional impairment. Overall, we found no association between amalgam exposure and neurological signs or clinically evident peripheral neuropathy. Our findings do not support the hypothesis that exposure to amalgam produces adverse, clinically evident neurological effects.

Dental Amalgam↗

Effect of partial recording protocols on estimates of prevalence of periodontal disease.

BACKGROUND: The aim of this study was to assess the degree of underreporting in the estimates of prevalence of periodontal attachment loss due to different partial recording protocols (PRP) in epidemiological studies, and to derive a correction factor to adjust for this bias. METHODS: The study sample included 1,460 dentate persons 14 to 103 years old who were examined clinically to assess the clinical attachment loss at six sites per tooth. Seven PRP based on full-mouth or half-mouth designs were assessed, and the bias and sensitivity in the assessment of attachment loss prevalence for these protocols were assessed. RESULTS: All partial protocols underestimated the prevalence of attachment loss. Bias estimates for any full-mouth PRP were smaller than those for the corresponding site-combination PRP for the half-mouth design. The PRP using the mesio-buccal (MB), mid-buccal (B), and disto-lingual (DL) sites of teeth in all four quadrants showed the smallest bias and highest sensitivity of prevalence estimates among the seven PRP evaluated, uniformly across the range of attachment loss severity level. The three site PRP incorporating the DL site produced less bias than the three site PRP including the disto-buccal (DB) site. There was a 3% to 12% gain in sensitivity for 2 to 5 mm attachment loss thresholds for the three site half-mouth PRP compared with the two site MB, B half-mouth PRP. CONCLUSIONS: The bias in the assessment of attachment loss is influenced by the partial recording design and the type and number of sites assessed, and is also influenced by the severity of attachment loss in the study population. These factors should be considered when selecting a partial recording method in large surveys. Furthermore, inflation factors designed to adjust for the bias due to the use of partial systems should be calculated and reported so that comparisons of results with other surveys are more meaningful.

Adolescent↗

Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome.

OBJECTIVE: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS). METHODS: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate. If 14 consecutive subjects on DHEA did not respond, a Phase III trial would be considered futile. A placebo group of 14 subjects was planned to verify placebo response rate and estimate sample size required for a definitive trial. Response criteria required 20% improvement in at least 2 of 3 domains. Analysis of covariance was used to adjust for baseline differences and for stratified randomization. Outcome measures included visual analog scale questionnaires for dry eye and dry mouth symptoms, lissamine green ocular dye staining and Schirmer I tests, stimulated salivary flow, IgG, and erythrocyte sedimentation rate (ESR). RESULTS: Randomization resulted in 14 DHEA and 14 placebo group subjects. At baseline, mean +/- SD for DHEA versus placebo groups were Schirmer I tests 4.5 +/- 4.5 versus 5.4 +/- 6.1 mm/5 minutes; Van Bijsterveld score 5.3 +/- 2.1 versus 5.5 +/- 2.2; unstimulated saliva 0.03 +/- 0.05 versus 0.04 +/- 0.10 ml/minute; IgG 1,699 +/- 749 versus 1,712 +/- 621 g/dl; and ESR 40 +/- 31 versus 44 +/- 28 mm/hour. Apart from changes over the trial in dry mouth symptoms, no significant differences were noted between the DHEA and placebo groups for dry eye symptoms, objective measures of ocular dryness, stimulated salivary flow; IgG, or ESR. Four DHEA and one placebo group patient dropped out because of adverse effects. Although 7 subjects met response criteria in the DHEA group, 5 met the criteria in the placebo group, and there was no significant difference between groups. CONCLUSION: DHEA showed no evidence of efficacy in SS. Without evidence for efficacy, patients with SS should avoid using unregulated DHEA supplements, since long-term adverse consequences of exposure to this hormone are unknown.

Adjuvants, Immunologic↗

Bone formation in transplants of human bone marrow stromal cells and hydroxyapatite-tricalcium phosphate: prediction with quantitative CT in mice.

PURPOSE: To determine whether quantitative computed tomography (CT) can be used to estimate the extent of new bone formation in hydroxyapatite-tricalcium phosphate (HA-TCP)-based transplants. MATERIALS AND METHODS: Bone-forming transplants were generated by attaching cultured human bone marrow stromal cells to aliquots of HA-TCP particles and were placed in subcutaneous pockets in immunocompromised mice. After 8 weeks, the transplants were individually imaged; each scan included a phantom. Overall bone mineral density (BMD) of each transplant was obtained. Hematoxylin-eosin-stained sections of the same transplants were then examined histologically, which is the reference standard for assessing bone formation. The extent of bone in each transplant was scored on a semiquantitative scale ranging from 0 to 4 by three independent blinded observers; the bone score for each transplant was calculated by averaging the three observer scores. BMD was compared with the histologically determined bone score for each transplant. Statistical evaluations included (a) calculation of empiric receiver operating characteristic curves to determine optimum BMD thresholds and (b) determination of the relationship between BMD and bone score, including derivation of Pearson correlation coefficients. RESULTS: One hundred twenty transplants were evaluated. Average BMD of 600 mg/cm3 K2HPO4 or more was noted in transplants with appreciable bone formation (bone score > or = 3), while average BMD of less than 600 mg/cm3 K2HPO4 was seen in transplants with poor bone formation (bone score < 3) (P <.001). Among transplants with appreciable bone formation, the BMD was proportional to the extent of mineralized matrix present in the new bone. CONCLUSION: Use of quantitative CT offers a practical approach for the noninvasive determination of new bone formation in mineralizing bone marrow stromal cells and HA-TCP transplants.

Animals↗

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.

Adult↗

Dental characteristics of fibrous dysplasia and McCune-Albright syndrome.

OBJECTIVE: Fibrous dysplasia (FD) is a skeletal disorder often associated with McCune-Albright syndrome, a rare multisystem disorder caused by GNAS1 gene mutation. FD frequently affects the craniofacial bones, including the maxilla and the mandible; nevertheless, its effects on dental tissues and the implications for dental care remain unclear. The aim of this study was to characterize the dental features associated with FD and the reaction of affected bones to routine dental therapy. Study design Thirty-two patients with FD underwent dental evaluation and endocrine testing as part of the diagnosis of FD/McCune-Albright syndrome. Any dental anomalies were recorded, and the associations between endocrinopathies and dental anomalies were analyzed statistically by means of the paired t test. RESULTS: Eighty-four percent had FD in the maxilla and/or mandible; endocrine dysfunction; and/or renal phosphate wasting. The caries index scores were 2.9 (ages 4-17 years) and 9.6 (ages 18-50 years). Malocclusion (81%) and other prevalent dental anomalies (41%) included tooth rotation, oligodontia, and taurodontism. The expansion of the maxilla or mandible by FD did not distort the dental arch curvature, and routine dental therapies such as extractions, restorations, and orthodontic treatment did not exacerbate FD lesions. CONCLUSION: Maxillomandibular FD was associated with higher rates of caries and malocclusion than were present in healthy patients. Furthermore, patients with FD did not require special dental management and were able to undergo routine dental care without an exacerbation of FD lesions.

Adolescent↗

Clinical evaluation of patients with temporomandibular joint implants.

PURPOSE: An undetermined number of patients with temporomandibular joint (TMJ) symptoms have been treated with intra-articular disc implants composed of Teflon ethylene/propylene or Teflon polytetrafluoroethylene and aluminum oxide (Proplast-Teflon; Vitek, Houston, TX). These implants have shown the potential to fragment in situ resulting in nonbiodegradable particles that stimulate a giant cell reaction and lead to degeneration of local structures, pain, and limitation of mandibular opening. We examined the possible relationship between TMJ implants and persistent pain, responses to sensory stimuli, quality of life, and systemic immune dysfunction. PATIENTS AND METHODS: This case series (32 patients) were referred from university-based orofacial pain centers and private practices from across the United States. Laboratory and clinical assessments evaluated orofacial pain symptoms, neurologic function, clinical signs and symptoms of rheumatologic disease, physical function, systemic measures of immune function, and behavioral measures. RESULTS: We found that TMJ implant patients appeared to have altered sensitivity to sensory stimuli, a higher number of tender points with a diagnosis of fibromyalgia, increased self-report of chemical sensitivity, higher psychologic distress and significantly lower functional ability. Systemic illness or autoimmune disease was not evident in this series of TMJ implant patients. CONCLUSIONS: Significant problems were noted on clinical assessment of TMJ implant patients. This is a US government work. There are no restrictions on its use.

Adult↗