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Biomedical subjects

J D Beck

Publications and source records attributed to J D Beck.

At least 91 records · Page 5Linked to original sources

Assessing dental anxiety, dental care use and oral status in older adults.

This study examined associations between dental anxiety and dental care use and oral health status in dentate older adults. Analysis of data from the Piedmont 65+ Dental Study revealed that aspects of dental care use and oral health status were independently associated with high dental anxiety. These results suggest that measures to control dental anxiety may help to improve dental care use and oral health status in older adults.

Aged↗

The design and implementation of trials of host modulation agents.

Over the last two decades it has become more evident that although oral microorganisms are essential agents of periodontal pathogenesis, interpatient variability in the host response is a major determinant of the expression of periodontal disease extent and severity. Data from animal models and human studies have identified many of the components of the host inflammatory response which serve as critical mediators of clinical inflammation, attachment loss, and bone resorption. Studies suggest that certain pharmacologic agents, which act at a molecular level to block specific inflammatory mediators, appear to attenuate disease progression. These promising findings herald a new era in periodontal medicine. Anti-infective therapies may soon be supplemented with anti-inflammatory pharmacological agents. However, there are many unanswered issues regarding formulation design, clinical application, potential indication claims, and clinical study design. Furthermore, current considerations of fundamental mechanisms of pathogenesis, as well as new data from epidemiologic studies emphasizing the multifactorial nature of disease, are changing the underlying assumptions which have served to guide our design of anti-infective drug trials over the last two decades. There are new questions regarding appropriate outcome measurements which are to be reconsidered. For example, the measurement of a change in periodontal disease status, either during progression or in response to therapy, is fundamentally unidimensional and may be only mildly informative when one considers that the disease is multifactorial by nature. Using an example from intensive care medicine, pathophysiologic studies of septic shock have demonstrated that the microbial dose and the host inflammatory mediator response are far better predictors of patient morbidity and mortality than any combination of clinical signs associated with clinical shock. Clinical trials of anti-cytokine and anti-inflammatory drugs to treat shock are now designed and conducted taking strategic advantage of this knowledge by including measurements of microbial dose and host response. It appears prudent that the design and implementation of clinical trials of host modulation agents also benefit from our current insights into pathogenesis and not represent a template-driven adaptation of historical, anti-infective clinical trial protocols.

Anti-Infective Agents↗

The structure of the human ALL-1/MLL/HRX gene.

The human ALL-1/MLL/HRX gene on chromosome 11q23 is the site of many locally clustered chromosomal alterations associated with several types of acute leukemias, including deletions. partial duplications and reciprocal translocations. Structurally variant proteins derived from an altered ALL-1 gene presumably make essential contributions to the malignant transformation of hematopoietic progenitor cells. The ALL-1 gene is spread over approximately 92 kb and consists of at least 37 exons. An exon/intron map including the position of the 3'-end of the gene and a detailed restriction map were produced and an updated map is presented. Data from other laboratories were incorporated where compatible. Exon/intron boundaries were sequenced and an intron-phase analysis was performed. The results are expected to contribute to a better understanding of those structural alterations of the gene that conserve the open reading frame and produce presumably oncogenic variants of the ALL-1 protein. They will also facilitate the rapid molecular diagnosis of structural alterations of this gene and the choice of therapeutic options. Mechanisms that may potentially account for the striking clustering of the translocation breakpoints in the breakpoint cluster region of the gene are discussed.

Base Sequence↗

A specific deletion in the breakpoint cluster region of the ALL-1 gene is associated with acute lymphoblastic T-cell leukemias.

A variety of chromosomal translocations to the ALL-1 gene are regularly observed in acute leukemias and are thought to play a key role in the leukemogenic process. Chimeric proteins are encoded by the breakpoint regions of the derivative chromosomes have been proposed to be the relevant oncogenic agents. In addition, internal duplications of the ALL-1 gene have been observed in patients with specific acute myeloid leukemias. Thus, it has been hypothesized that oncogenic variants of the ALL-1 protein may be generated by both chimerization and self-fusion, but the critical structural features endowing the altered proteins with their oncogenic potential are still unknown. Here a novel structural alteration of the ALL-1 gene was observed in three patients presenting with acute T-cell leukemia (ALL) without chromosomal translocations or self-fusions of the ALL-1 gene. These unrelated patients carried an internal deletion in one of the two alleles of the ALL-1 gene that eliminated parts of introns 7 and 8, together with exon 8. The deletion was found in 3 of 74 ALL patients, but not in acute myeloid leukemias, follicular lymphomas, or peripheral blood leukocytes from healthy donors. One ALL patient showed the deletion at diagnosis but no longer at remission or at 9 months after remission. These findings support the hypothesis that the ALL-1 protein may be converted to an oncogenic variant, not only by chimerization or self-fusion, but also by deletion of sequences coded by exon 8. They further suggest that these three different types of structural alterations of the ALL-1 protein may each cause a distinct disease phenotype. Alternatively spliced mRNA species omitting exon 8 were observed in 14 of 24 ALL patients without detectable macroscopic alterations of the ALL-1 gene and also in peripheral blood leukocytes from healthy donors.

Adolescent↗

Quantitative EEG in long-term survivors of acute lymphoblastic leukemia.

Conventional and quantitative aspects of electroencephalographic recordings obtained during a follow-up surveillance study in long-term survivors of acute lymphoblastic leukemia in childhood were investigated with respect to differences in central nervous system prophylaxis given during antileukemic therapy and compared with data derived from healthy controls. Central nervous system prophylaxis consisted either of cranial irradiation (18 Gray, group A, n = 8) or intermediate high-dose methotrexate (2000 mg/m2; group B, n = 5), each combined with intrathecal methotrexate. Conventional electroencephalographic analysis revealed comparable results in all three study groups. However, quantitative electroencephalography showed significantly increased absolute power scores for all frequency bands in both long-term survivor groups. Relative power estimates revealed a significant increase in delta/tau activities in both prophylaxis groups compared to healthy controls, which were countered by decreased percentage power scores in the alpha-range. Quantitative electroencephalographic comparisons between both central nervous system prophylaxis groups revealed only small differences in quantity, not quality, of the observed power disturbances with slightly higher deviations in irradiated long-term survivors than in nonirradiated ones. Topographical distributions of spectral band power were comparable between all three study groups without evidence for therapy-related topographical differences.

Adolescent↗

Ten-year longitudinal study of periodontal attachment loss in healthy adults.

Despite much research, it is still difficult to make generalizations concerning aging and periodontal diseases. This study examined 95 healthy men and women (aged 29 to 76 years at initial visit) from the oral physiology component of the Baltimore Longitudinal Study of Aging over a 10-year period. Periodontal measurements were taken at two visits, and recession, pocket depth, and level of attachment determined. The change of level of attachment and attachment loss was assessed as a longitudinal measure of disease progression. Overall there were only slight changes in periodontal measurements over the 10-year period. Attachment loss was age-dependent and was due primarily to increased recession not to changes in pocket depth. Periodontal disease destruction (as measured by attachment loss) occurred over time but was not related to the age or gender of a person. These results from healthy persons suggest that periodontal diseases are not a natural consequence of the aging process, and that advanced age is not an accurate predictor of attachment loss.

Adult↗

Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias.

The acute lymphoblastic leukaemia (ALL)-1 gene on human chromosome 11q23 is the site of many locally clustered chromosomal alterations associated with several types of acute leukaemias, including deletions, partial duplications and translocations. Structurally variant proteins derived from the altered gene presumably cause the malignant transformation of early haemopoietic progenitor cells. According to previously published reports, the gene consisted of at least 21 exons spread over approximately 100 kb. In this report a set of genomic fragments was isolated that represent a total of 35 exons (exons 3-37) encompassing > 95% of the protein-coding region (except exons 1 and 2) and the 3'-non-translated region of the gene. The distances between these exons were determined and a detailed restriction map was produced. The majority of the exon/intron boundaries were sequenced and an intron-phase analysis was performed. The results form the basis for a greater understanding of the translocations and other structural alterations of the gene that conserve the open reading frame and thus produce presumably oncogenic variants of the ALL-1 protein.

Base Sequence↗

P300 abnormalities in long-time survivors of acute lymphoblastic leukemia in childhood--side effects of CNS prophylaxis?

The incidence and the degree of P300 abnormalities in relation to psychometric findings was assessed in two groups of long-term survivors of acute lymphoblastic leukemia (ALL) in childhood. The study was performed as part of a follow-up trial, evaluating CNS late-effects after antileukemic therapy, 7.1 +/- 1.6 years after cessation of antileukemic therapy. Subject groups differed primarily in terms of antileukemic CNS prophylaxis: combined radio- and chemotherapy (n = 8) vs. chemotherapy alone (n = 5). Results were compared with those of a third group of healthy controls (n = 13) matched for age and gender. P300 recordings were obtained during a visual oddball-paradigm using checkerboard reversal stimuli of different pattern sizes as target and background events. Neurophysiological data were correlated with the results of a psychological test battery, which measured general intelligence, non-verbal visual memory functioning and concentration. ERP analysis showed a significant prolongation of the P300 latency in irradiated subjects when compared to healthy controls and non-irradiated long-term survivors. Topographical data comparisons revealed substantial P300 differences in both ALL long-term survivor groups when compared with healthy controls. This demonstrated significantly lower amplitudes over the left frontal derivations, associated with lowered concentration abilities, in the irradiated subject group. Higher amplitudes over the parieto-temporal derivations of the right hemisphere, associated with significantly impaired visual memory capabilities, were seen in both long-term survivor groups.

Adolescent↗

Visual-evoked potentials in long-term survivors of acute lymphoblastic leukemia in childhood. The German Late Effects Working Group.

Visual-evoked potentials (VEPs) were studied in 92 asymptomatic long-term survivors of acute lymphoblastic leukemia (ALL) in first complete remission 6-7 years after cessation of therapy in order to detect therapy-related disturbances in conduction velocity capacities within central nerve fibers. Subjects were grouped with respect to CNS prophylaxis: a) ith. MTX and 18 GY cranial irradiation (group A, n = 58), b) ith. MTX and iv. MHD-MTX, no cranial irradiation (group B, n = 34). At follow-up VEPs were abnormal in 10 subjects (10.9%) with comparable rates in both CNS prophylaxis groups (A: 7/58 [12.1%], B: 3/34 [8.8%]; p = 0.56). Participants with radiological signs of leukodystrophy (n = 14), all within the irradiated CNS prophylaxis group showed significantly prolonged P100 latencies and had a 6.1-fold increased relative risk to develop VEP disturbances. No correlation could be established between VEP outcome and illness- or treatment-related parameters. VEP outcome was not correlated with age at diagnosis or gender. Thus, VEP recordings showed a close relationship with radiation-induced CNS white-matter disturbances. However, their value for clinical practice, routinely performed follow-up evaluations or standardized posttreatment surveillance studies is negligible.

Age of Onset↗

Postoperative radiotherapy of medulloblastoma. Impact of radiation quality on treatment outcome.

Between 1975 and 1991, 40 patients with newly diagnosed medulloblastoma of the posterior fossa were treated at the authors' institutions. After aggressive surgical resection 39/40 patients (98%) received craniospinal radiation therapy (RT), including a local boost. A group of 29 patients was treated with adjuvant chemotherapy. The estimated overall 5-year survival and 5-year relapse-free survival (RFS) probabilities were 75% and 65%, respectively. The 5-year survival was significantly prolonged for patients treated after 1981 as compared to those treated between 1975 and 1980 (80% vs 64%, p = .02). However, multivariate analysis identified the adequate coverage of the target volume by external RT as the only significant variable (p = .0031). The extent of resection, stage according to Chang, radiation dose to the posterior fossa (< 55 Gy vs > or = 55 Gy) and the use of chemotherapy did not significantly influence survival and RFS. The initial site of recurrence was the posterior fossa with or without disseminated central nervous system (CNS) disease in 5 patients, the CNS without posterior fossa in 4 patients, and the bone marrow in 2 patients. An isolated frontal relapse occurred in 1 patient. We conclude that quality control of RT plays a decisive role in the long-term outcome of patients with medulloblastoma.

Adolescent↗

The impact of new technologies to diagnose and treat periodontal disease. A look to the future.

The last 25 years have brought unprecedented advances to our understanding of periodontal disease. Consider that in 1970 periodontitis was believed to effect most individuals over the age of 35 years, to progress steadily in an individual once initiated until teeth were lost, to be the primary cause of tooth loss in adults, to be caused by the bacterial mass accumulating on the tooth surface and subgingivally, and to involve the host in some fashion or another. In the 25 years since then, impressive research advances in the epidemiology of periodontal disease, the specific bacterial etiology of periodontal disease and the immunoinflammatory mediators of periodontal tissue destruction have greatly altered our view of periodontal disease. Thus, given these research advances in the understanding of periodontitis, what may the future hold for improved diagnosis and treatment of periodontal disease? Impressive research into new ways to diagnose the periodontal diseases is well underway. Investigators are seeking new ways to diagnose an individual's degree of risk for periodontal disease initiation, susceptibility to disease progression, level of disease "activity" and the likely response to treatment and recurrence of active disease. New diagnostic tests should greatly advance our ability to more accurately and specifically diagnose periodontal disease. The future also looks promising for new treatment strategies to slow or arrest periodontal disease progression. The bacterial specificity of periodontal disease etiology revealed since 1970 has logically led to the use of antibiotics in periodontitis treatment. In the late 1980s the concept of locally delivering antibiotics to the periodontal pocket was introduced, and subsequent clinical trials have indicated that it is possible to reduce pocket depth and inflammation with tetracycline locally delivered to the periodontal pocket. Likely, we have barely scratched the surface in studying the efficacy of locally delivery antimicrobial agents to alter the progression of periodontal disease. As new agents are developed and better delivery systems to the periodontal pocket are developed, the future should see a variety of antimicrobial agents available which can slow periodontal disease progression. The future also holds promise for slowing periodontal disease progression by blocking inflammatory pathways important in periodontal tissue destruction. Clinical trials of flubiprofen, naproxen and ketoprofen indicate that it is possible to slow periodontal disease progression with non-steroidal anti-inflammatory drugs which inhibit one destructive pathway. In addition, data from animal models indicate that chemically modified tetracycline as an inhibitor of collagenase can slow disease progression in animals. Again, we have likely only just begun to explore the wide range of molecular mediators of tissue destruction which may be targeted for blocking and thereby slow or arrest periodontal disease progression. Last, research into regenerating periodontal structures lost as a result of disease has had a noteworthy record of progress in the past 25 years. Techniques that utilize bone grafts, root treatments, tissue guiding membranes or polypeptide growth factors have ably indicated that it is possible to regenerate new attachment structures in humans. As investigators continue to unravel the mysteries of the embryonic development of the periodontium, the ability to predictably regenerate lost periodontal attachment structures holds great promise for the future.

Adult↗

Adjustment of the M-component of the DMFS index for prevalence studies of older adults.

Cross-sectional studies of caries in older adults report a substantial number of missing teeth, making it difficult to estimate caries experience accurately. The goal of this study was to improve the method of estimating caries experience as expressed by the DMFS index in population groups with missing teeth. The adjustment was demonstrated with reference to the Piedmont 65+ Dental Study conducted on a random sample of 363 community-dwelling older adults in North Carolina who were followed for 5 years. These older dentate adults had a mean (+/-SE) of 11.7 +/- 0.5 teeth missing at baseline, 56.1 +/- 2.5 missing surfaces and a DMFS of 86.7 +/- 2.0. A predicted caries prevalence was determined from the DFS at 5 yrs plus the 5-yr DFS incidence and the baseline DFS of teeth lost during the study period. Then a formula was developed that would estimate the predicted caries prevalence as a function of the observed 5-yr DMFS. This formula provided a good estimation of caries prevalence at 5 yrs (DMFSadj) when compared with the predicted prevalence (paired t-test, p > 0.05), while prevalence was underestimated by the DFS and greatly overestimated by the traditional DMFS index. Subgroup analyses by race, sex, and periodontal status also indicated that the DMFSadj resulted in patterns of estimates similar to the predicted prevalence, while the DFS and the DMFS were likely to result in different findings. The DMFS from the time of tooth eruption also was adjusted using this formula. The resulting analyses of subgroup differences in caries were not different from the previous estimates based on the 5-yr historical data, indicating that the adjustment of all M surfaces avoids the biases inherent in the traditional DMFS and DFS indices. This study showed that predicted caries prevalence could be estimated by adjusting the M component of the DMFS. It appears that this adjustment formula can be used without obvious bias, but additional studies are needed to provide adjustment figures for populations with different caries prevalences.

Black or African American↗

Five-year incidence rates and intraoral distribution of root caries among community-dwelling older adults.

The 5-year incidence and intraoral distribution of decayed and filled root surfaces were evaluated in 379 black and 323 white residents of North Carolina aged 65 and older. During the period of study, approximately 39% of blacks developed at least one root DFS compared with 52% for whites (Wald X(2) test, p = 0.062). When the results were calculated using the net root DFS increment, blacks did not have significantly higher rates than whites over the 5-year study period (0.52 surfaces/person versus 0.42 surfaces/person, Survey Regression, n = 363, p = 0.708). However, for blacks, the 5-year incidence density rate of root DFS was 0.26 per 60 surface-months at risk, and for whites the rate was 0.19 new root DFS per 60 surface-months (incidence density ratio = 1.33, 95% CI = 1.01-1.76, p = 0.047). Intraoral distribution patterns for root caries incidence revealed that the approximal surfaces of the anterior teeth were involved most frequently, particularly in the mandible and maxilla in whites, followed in decreasing order by the buccal surfaces of the lower anteriors and the mesial surfaces of the upper anteriors in blacks. Although root caries incidence rates were obviously low, there were significant differences in the occurrence of caries between blacks and whites. The pattern of occurrence was similar for both races with root surface disease being concentrated in the approximal surfaces of the anterior teeth in a small proportion of affected individuals, with whites presenting more filled root increments than blacks. These findings suggest a need for more caries treatment in blacks and increased monitoring of this population since they are at a higher risk for root caries.

Black or African American↗

Variations in the social impact of oral conditions among older adults in South Australia, Ontario, and North Carolina.

Previous studies among older adults have demonstrated that oral disease frequently leads to dysfunction, discomfort, and disability. This study aimed to assess variations in the social impact of oral conditions among six strata of people aged 65 years and older: residents of metropolitan Adelaide and rural Mt Gambier, South Australia; residents of metropolitan Toronto-North York and non-metropolitan Simcoe-Sudbury counties, Ontario, Canada; and blacks and whites in the Piedmont region of North Carolina (NC), United States. Subjects were participants in three oral epidemiological studies of random samples of the elderly populations in the six strata. Some 1,642 participants completed a 49-item Oral Health Impact Profile (OHIP) questionnaire which asked about impacts caused by problems with the teeth, mouth, or dentures during the previous 12 months. The percentage of dentate people reporting impacts fairly often or very often was greatest among NC blacks for 41 of the OHIP items. Two summary variables of social impact were used as dependent variables in bivariate and multivariate least-squares regression analyses. Among dentate people, mean levels of social impact were greatest for NC blacks and lowest for NC whites, while people from South Australia and Ontario had intermediate levels of social impact (P < 0.01). Missing teeth, retained root fragments, root-surface decay, periodontal pockets, and problem-motivated dental visits were associated with higher levels of social impact (P < 0.05), although there persisted a two-fold difference in social impact across the six strata after adjustment for those factors Among edentulous people, there was no statistically significant variation in social impact among strata. The findings suggest that there are social and cultural factors influencing oral health and its social impact, and that those factors differ most between dentate blacks and whites in NC.

Black or African American↗

Exploratory case-control analysis of psychosocial factors and adult periodontitis.

We explored the association between social factors and adult periodontitis by comparing self-reported information for daily strains and symptoms of depression in 71 cases and 77 controls. Cases and controls were selected from among 1,426 participants in the Erie County Risk Factor Study. We found differences among those who scored higher than their peers on measures of social strain. The odds ratio (OR) and 95% confidence interval (95% CI) for the association between case status and Role Strain score of 2.27 or more was 2.84, 95% CI = 1.08 to 7.46. We also examined serum antibody, dichotomized at the median, for three periodontal pathogens (Bacteroides forsythus [IgG Bf], Porphyromonas gingivalis [IgG Pg], Actinobacillus actinomycetemcomitans [IgG Aa]), and assessed interaction between antibody levels and a Depression score derived from the Brief Symptom Inventory. IgG Pg and IgG Aa were both strongly associated with case status (OR = 4.52, 95% CI = 1.99 to 10.3 and OR = 5.29, 95% CI = 2.34 to 12.0, respectively). IgG Bf was associated with periodontal disease but only among individuals who had higher scores for Depression (OR = 6.75, 95% CI = 1.25 to 36.5). Smoking status was associated with case status (OR = 4.95, 95% CI = 1.86 to 13.2). We assessed these findings prospectively by examining factors associated with more extensive disease among the 71 case subjects after 1 year of follow-up. We found baseline smoking status and IgG Bf among individuals scoring high on Depression at baseline to be associated with more extensive disease (8.1% or more of the sites showing further breakdown). In this population an elevated Depression score may be a marker for social isolation, which could play a role in immune function during periods of social strain. This exploratory analysis has served to identify specific lines of inquiry concerning psychosocial measures as important environmental factors in adult periodontitis.

Adult↗

Stem cell separation in paediatric patients.

We performed 28 separations in 11 children weighing from 14 to 72 kg (median: 27 kg) using either the Cobe Spectra or the Fresenius AS 104 cell separator. For children under 20 kg, human albumin solution was used for the last 200 mL of the priming procedure instead of NaCl. Blood flow was reduced to 30-50 mL min-1 depending on the children's size and weight to prevent citrate reactions. Within 149-337 min we processed three times the patients' total blood volume and collected 309.7 x 10(6) (102.9-1140.0) mononuclear cells (MNC) and 2.01 x 10(6) (1.90-6.50) CD34+ cells per kg body weight. These results were comparable to the results we previously obtained in adults. We conclude from these initial results that peripherae blood stem cells (PBSC) separations, with both devices, can be adapted successfully to the needs of paediatric patients.

Antigens, CD34↗

Epidemiology of periodontal diseases.

This review summarizes findings from 46 reports selected from over 130 epidemiologic studies published in 1993 and 1994. Recent findings from longitudinal studies are consistent with the concept that periodontal destruction proceeds in random bursts at specific sites and demonstrate that some individuals have an elevated risk of attachment loss. These and other studies provide further evidence that cigarette smoking is a significant risk factor. New studies have quantified the risk of tooth loss due to periodontal disease, and there is better knowledge about HIV-associated periodontal diseases. Familial studies suggest that both environmental and genetic factors contribute to individual variations in etiologic factors (such as plaque) and periodontal diseases. Several studies propose an intriguing link between periodontal diseases and coronary heart disease, which may be mediated through risk factors common to both diseases, and as a direct consequence of the contribution of periodontal bacteria and their products to atherosclerosis.

Arteriosclerosis↗