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Biomedical subjects

A M Best

Publications and source records attributed to A M Best.

At least 19 recordsLinked to original sources

Predictors of nutritive sucking in preterm infants.

OBJECTIVE: The purposes of this analysis were to determine how select characteristics of nutritive sucking (number of sucks, sucks/burst, and sucks/minute) change over time and to examine the effect of select factors (morbidity, maturity, prefeeding behavior state, and feeding experience) on those changes. STUDY DESIGN: A longitudinal, non-experimental study was conducted in a Level 3 neonatal intensive care unit using a convenience sample of 88 preterm infants. Statistical analyses were performed using a repeated-measures mixed-model in SAS. RESULTS: Sucking activity (number of sucks, sucks/burst, and sucks/minute) was predicted by morbidity, maturity, feeding experience and prefeeding behavior state. Experience at oral feeding had the greatest effect on changes in the number of sucks, suck/burst and sucks/minute. CONCLUSION: Experience at feeding may result in more rapid maturation of sucking characteristics.

Bottle Feeding↗

The pulpal origin of immunoglobulins in dentin beneath caries: an immunohistochemical study.

Immunoglobulins localized in uninfected dentin beneath caries are thought to be protective, but their origin remains controversial. We reasoned that the localization and dominance of serum IgG1 would support the pulpal origin of the immunoglobulins while a predominance of secretory component (SC) bearing IgA1 and IgA2 would support their salivary origin. The prevalence and staining intensity of IgG1, IgA1, IgA2, IgM, and SC in uninfected dentinal tubules beneath shallow, deep caries, and noncaries teeth were examined immunohistologically. SC was only localized in caries, and IgG1 was the predominant subclass in uninfected dentinal tubules beneath shallow and deep caries, followed by IgA1. In noncaries teeth, IgG1 was localized on the pulpal end. The intensity of IgG1 was significantly higher than either IgA1 or IgA2 in both shallow and deep caries. Our data support the serum origin of immunoglobulins in uninfected dentin beneath caries.

Analysis of Variance↗

Thrombin generation time is a novel parameter for monitoring enoxaparin therapy in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) who receive enoxaparin are at increased risk for adverse bleeding episodes. This phenomenon appears to occur despite judicious monitoring of antifactor Xa (aFXa) activity. Better monitoring parameters are needed to quantify the anticoagulant effects of enoxaparin in the ESRD population. OBJECTIVES: The objective of this study was to determine the utility of using thrombin generation time (TGT), platelet contractile force (PCF) and clot elastic modulus (CEM) to monitor the degree of anticoagulation in ESRD subjects, and to compare these results to aFXa activity, the current gold-standard monitoring parameter. METHODS: Eight healthy volunteers without renal dysfunction and eight ESRD subjects were enrolled into this study. Subjects received a single dose of enoxaparin 1 mg kg(-1) subcutaneously, and blood samples were obtained for the determination of aFXa activity, TGT, PCF and CEM at baseline, 4, 8, and 12 h postdose. RESULTS: Baseline, 4, 8, and 12-h aFXa activity concentrations were not different between groups. However, the corresponding TGT at 8 and 12 h was significantly prolonged in the ESRD group (P = 0.04, and P = 0.008, respectively). The 4-h peak TGT trended toward significance (P = 0.06). There were no differences in PCF or CEM across time. CONCLUSIONS: These data suggest that the parameter aFXa activity is a poor predictor of the anticoagulant effect of enoxaparin in patients with ESRD. Thrombin generation time appears to be more sensitive to the antithrombotic effects of enoxaparin in this population. Further large-scale trials are needed to corroborate these data.

Adult↗

Lorazepam concentrations, pharmacokinetics and pharmacodynamics in a cohort of mechanically ventilated ICU patients.

OBJECTIVES: To evaluate plasma concentrations, pharmacokinetics and pharmacodynamics of lorazepam in a cohort of mechanically ventilated patients. INTERVENTIONS: Patients underwent simultaneous measurement of lorazepam concentration and sedation assessments using the Sedation-Agitation Scale (SAS) and Bispectral Index (BIS). Lorazepam administration was classified as either continuous intravenous infusion (CIVS) or bolus. MAIN RESULTS: A total of 124 observations were made in 13 patients. The median concentration was 59 ng/ml, interquartile range 23 - 93 ng/ml, range 0 - 1,072 ng/ml. Clearance was preserved at 92 +/- 71 ml/min. Higher concentrations were associated with deeper sedation determined by both SAS and BIS. Two patients were managed with CIVS and received more lorazepam than those managed without (288 +/- 53.5 versus 55 +/- 25.2 mg, p-value < 0.005). CIVS administration was associated with higher concentrations (629 +/- 36 versus 49 +/- 15 ng/ml, p-value < 0.001) and deeper sedation by both SAS and BIS. CONCLUSIONS: Lorazepam clearance was preserved with a wide range of concentrations. Higher concentrations were associated with deeper sedation and use of CIVS. Elevated concentrations during CIVS were attributable to administration of larger doses.

Cohort Studies↗

Antifactor Xa activity correlates to thrombin generation time, platelet contractile force and clot elastic modulus following ex vivo enoxaparin exposure in patients with and without renal dysfunction.

Antifactor Xa activity is the gold standard monitoring parameter for low molecular weight heparin (LMWH) derivatives. It is frequently measured in high-risk populations, such as patients with renal dysfunction. Despite antifactor Xa monitoring, however, bleeding in renal dysfunction patients receiving LMWH remains a problem. This study determined the relationship between antifactor Xa activity and three novel coagulation monitoring parameters: thrombin generation time (TGT), platelet contractile force (PCF) and clot elastic modulus (CEM). This study also assessed the effect of renal dysfunction on these relationships. This was an ex vivo pharmacodynamic study of the relationship between antifactor Xa activity and TGT, PCF and CEM in subjects both with and without renal dysfunction. Thirty subjects completed this study (10 controls, 10 chronic kidney disease subjects, and 10 end-stage renal disease subjects receiving hemodialysis). Blood samples obtained from participants were spiked with increasing enoxaparin concentrations (0.25, 0.5, 1.0 and 3.0 IU mL(-1)). Samples were analyzed for TGT, PCF and CEM. The relationship between antifactor Xa activity and TGT, PCF and CEM was determined by Pearson's correlation. The effect of renal dysfunction on the relationship between antifactor Xa activity and TGT, PCF and CEM was determined by analysis of covariance. There is strong correlation between antifactor Xa activity and TGT, CEM and PCF. The presence of renal dysfunction significantly prolongs the TGT, and decreases the CEM relative to controls. These results suggest that patients with renal dysfunction have a greater pharmacodynamic response to LMWH, independent of the pharmacokinetics of LMWH.

Adult↗

Anti-cardiolipin antibodies in sera from patients with periodontitis.

Antiphospholipid antibodies are commonly found in patients with systemic lupus erythematosus or the antiphospholipid syndrome, and a subset of such antibodies is associated with prothrombotic events such as stroke and with adverse pregnancy outcomes and fetal loss. We examined sera from 411 patients who were clinically characterized as to their periodontal disease status for serum levels of beta2-glycoprotein I-dependent anti-cardiolipin autoantibodies (anti-CL). The prevalence of patients with chronic periodontitis (CP) and generalized aggressive periodontitis (GAgP) positive for anti-CL (16.2% and 19.3%, respectively) was greater than that in healthy controls (NP) and localized aggressive periodontitis (LAgP) patients (6.8% and 3.2%). Patients with these autoantibodies demonstrated increased pocket depth and attachment loss compared with patients lacking the antibodies. Analysis of the data indicates that patients with generalized periodontitis have elevated levels of autoantibodies reactive with phospholipids. These antibodies could be involved in elevated risk for stroke, atherosclerosis, or pre-term birth in periodontitis patients.

Adult↗

Impact of sociodemographic characteristics on the identification rates of minority students as having mental retardation.

Ethnic disproportionality among students with mental retardation and relationships between disproportionality and sociodemographic factors were investigated. Using national data, we examined the effects of gender, ethnicity, and sociodemographic factors on the proportion of students identified as having mental retardation. Results indicate a clear association among ethnicity, gender, and mental retardation. Sociodemographic variables were also strongly associated with the proportion of students identified. A logistic regression model that included sociodemographic predictors was significantly better than models with gender and race alone. Findings indicate that both individual student characteristics and district sociodemographic characteristics were important in determining the likelihood of identification of mental retardation and that the impact of the sociodemographic characteristics is different for each gender/ethnicity group. Recommendations for future research are provided.

Child↗

Non-redundant roles for interleukin-1 alpha and interleukin-1 beta in regulating human IgG2.

BACKGROUND: Serum concentrations of immunoglobulin G2 (IgG2) are elevated in localized aggressive periodontitis (LAgP) patients, and secretory products of monocytes from LAgP patients enhance IgG2 responses of lymphocytes from healthy subjects. Furthermore, genes regulating production of interleukin (IL)-1 influence the risk for both aggressive periodontitis (AgP) and chronic periodontitis. These observations, and the fact that IgG2 dominates responses to carbohydrates from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis, prompted the hypothesis that IL-1 alpha, IL-1 beta, and IL-RA may help regulate human IgG2 responses. METHODS: Human peripheral blood leukocytes (PBL) were stimulated in culture with pokeweed mitogen (PWM); the levels of available IL-1 gene products were manipulated; and the effect on IgG2 production was monitored. Manipulations of IL-1 were accomplished by adding specific neutralizing monoclonal antibodies or recombinant IL-1RA, IL-1 alpha, or IL-1 beta. RESULTS: Blocking the IL-1 receptor with IL-1RA or neutralizing IL-1 alpha or IL-1 beta with specific antibody dramatically suppressed IgG2 production (50% to 70%). Additionally IL-1 alpha did not compensate for neutralized IL-1 beta, and additional IL-1 beta did not compensate for neutralized IL-1 alpha, suggesting the 2 monokines have separate roles in promoting IgG2. Furthermore, combinations of anti-IL-1 alpha and anti-IL-1 beta were more inhibitory than either antibody alone, and IL-1 alpha and IL-1 beta in combination appeared to work additively in promoting IgG2. Moreover, PBL cultures from a group of LAgP patients with high IgG2 levels had elevated levels of IL-1 beta. CONCLUSION: IL-1 alpha and IL-1 beta appear to have critical and non-redundant roles in the generation and regulation of potent IgG2 responses, which appear to be important in human responses to carbohydrate-bearing bacteria.

Adult↗

Factors considered by new faculty in their decision to choose careers in academic dentistry.

To determine the characteristics of new dental faculty and what factors influenced them to choose academic careers, a survey was sent to deans at all U.S. dental schools to be distributed to faculty with length of service of four years or less. Responses were received from 240 individuals. About half of the respondents had been in private practice for an average of eight years, and 20 percent had military experience averaging almost sixteen years. A majority had postgraduate training and 60 percent had specialty training. Nearly 32 percent of new faculty were female and 80 percent were U.S. citizens. Analyses of responses to survey items indicated that correlated factors in the survey fell into the following empirical categories: teaching and scholarship, income and indebtedness, research, work schedule, influence of mentors and role models, and long-term aspirations. In general, the respondents identified factors relating to teaching and scholarship to be the most important influences on their choice of academic careers, while concerns about income and indebtedness were the most important negative considerations in this regard. Other positive factors identified by the survey related to the influence of mentors and role models, long-term aspirations, and research. Age, private practice experience, and military experience were found to particularly influence the new faculty members' responses to items concerning income and indebtedness, and citizenship influenced responses to factors relating to research. The data from this select group of dentists support the current view that inequities in income of dental faculty compared to private practitioners and student debt are important concerns in choosing academic careers. Importantly, the desire to teach and participate in scholarly activities are important attractions in academic careers. Mentoring activities and creation of opportunities for career development are crucial factors in developing interest in academics among graduate dentists.

Adult↗

Current trends in the treatment of maxillofacial injuries in the United States.

This report presents the results of a 1997 survey of the members of the America Association of Oral and Maxillofacial Surgeons to assess the current national and regional trends in the management of maxillofacial trauma. Comparisons are made with the nearly identical survey done in 1987. The results show practitioner age-related differences and changes in reported practice across time. The significance of these findings are discussed.

Fracture Fixation, Internal↗

Cytokine induction by Streptococcus mutans and pulpal pathogenesis.

Chronic pulpal inflammation under caries appears to be elicited by bacterial antigens that diffuse into the pulp through dentinal tubules. This prompted the hypothesis that cytokines elicited by antigens from Streptococcus mutans, which frequently dominates shallow lesions, could play a major role in eliciting the initial T-cell response in the pulp. To test this, we examined the ability of S. mutans to stimulate T cells and elicit cytokines and used Lactobacillus casei, which often predominates in deep carious lesions where B cells and plasma cells predominate, as a control. In addition, the presence of cytokines in the pulp was analyzed at the mRNA level. S. mutans elicited potent gamma interferon (IFN-gamma) responses in peripheral blood mononuclear cell cultures and reduced the CD4/CD8 ratio by promoting CD8(+) T cells. Multiple inflammatory cytokine mRNAs (IFN-gamma, interleukin 4 [IL-4], and IL-10) were detected in human dental pulp. A higher prevalence of IFN-gamma (67%) than IL-4 (19%) or IL-10 (29%) was obtained in shallow caries, suggesting a type 1 cytokine mechanism in early pulpitis where S. mutans predominates. In contrast, in deep caries no differences in cytokine frequency were observed. Furthermore, the presence of IFN-gamma in the pulp correlated with the presence of S. mutans. The extraordinary induction of type 1 cytokines and the preferential activation of CD8(+) T cells by S. mutans offers an explanation for the etiology of the CD8(+) T-cell-dominant lesion in early pulpitis and suggests that S. mutans may have a major impact on the initial lesion and pulpal pathology.

CD4-CD8 Ratio↗

Regulation of immunoglobulin G2 production by prostaglandin E(2) and platelet-activating factor.

Patients with localized juvenile periodontitis (LJP) have elevated levels of immunoglobulin G2 (IgG2) in their sera. This is also observed in vitro when peripheral blood leukocytes from LJP patients are stimulated with pokeweed mitogen. In previous studies, we showed that lymphocytes from subjects with no periodontitis (NP subjects) produced substantial amounts of IgG2 when they were cultured with monocytes from LJP patients (LJP monocytes). These observations indicate that monocytes or monocyte-derived mediators are positive regulators of the production of IgG2. The present study was initiated to determine if secreted factors from LJP monocytes were capable of enhancing IgG2 production and to determine if prostaglandin E2 (PGE(2)), which LJP monocytes produce at elevated levels, enhances IgG2 production. Experiments in a transwell system and with monocyte-conditioned media indicated that cell-cell contact was not necessary for LJP monocytes to augment the production of IgG2 by T and B cells from NP subjects. Moreover, the production of IgG2 was selectively induced by the addition of PGE(2) or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE(2) synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE(2), or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE(2), indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE(2) reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE(2) synthesis. Together, these data indicate that PGE(2) and PAF are essential for the production of IgG2.

Aggressive Periodontitis↗

A canarypox vector expressing cytomegalovirus (CMV) glycoprotein B primes for antibody responses to a live attenuated CMV vaccine (Towne).

To develop a vaccine against cytomegalovirus (CMV), a canarypox virus (ALVAC) expressing CMV glycoprotein (gB) was evaluated alone or in combination with a live, attenuated CMV vaccine (Towne). Three doses of 106.5 TCID50 of ALVAC-CMV(gB) induced very low neutralizing or ELISA antibodies in most seronegative adults. However, to determine whether ALVAC-CMV(gB) could prime for antibody responses, 20 seronegative adults randomly received either 106.8 TCID50 of ALVAC-CMV(gB) or 106.8 TCID50 of ALVAC-RG, expressing the rabies glycoprotein, administered at 0 and 1 month, with all subjects receiving a dose of 103.5 pfu of the Towne vaccine at 90 days. For subjects primed with ALVAC-CMV(gB), neutralizing titers and ELISA antibodies to CMV(gB) developed sooner, were much higher, and persisted longer than for subjects primed with ALVAC-RG. All vaccines were well tolerated. These results demonstrate that ALVAC-CMV(gB) primes the immune system and suggest a combined-vaccine strategy to induce potentially protective levels of neutralizing antibodies.

Adult↗

Antiphosphorylcholine antibody levels are elevated in humans with periodontal diseases.

Human immunoglobulin G2 (IgG2) serum concentrations and the IgG2 antibody response to Actinobacillus actinomycetemcomitans can be influenced by genes, by environmental factors such as smoking, and by periodontal disease status. Examination of the IgG2 response to phosphorylcholine (PC), a response thought to be mainly induced by the C polysaccharide of Streptococcus pneumoniae, suggested that periodontal disease status was also associated with this response. This prompted the hypothesis that PC is an important oral antigen associated with organisms in the periodontal flora and that anti-PC antibody is elevated as a consequence of periodontal disease. Subjects in various periodontal disease diagnostic categories in which attachment loss is exhibited were tested for anti-PC in serum. Those with adult periodontitis, localized juvenile periodontitis, generalized early-onset periodontitis, and gingival recession all had similar levels of anti-PC IgG2 serum antibody which were significantly greater than in the group of subjects with no attachment loss. Analysis of plaque samples from subgingival and supragingival sites in all diseases categories for reactivity with the anti-PC specific monoclonal antibody TEPC-15 revealed that a substantial proportion of the bacteria in dental plaque (30 to 40%) bear PC antigen; this antigen was not restricted to morphotypes resembling only cocci but was also present on rods and branched filamentous organisms. We found that S. mitis, S. oralis, and S. sanguis, as well as oral actinomycetes, including A. viscosus, A. odontolyticus, and A. israelii, incorporated substantial amounts of [(3)H]choline from culture media. Further analysis of antigens derived from these organisms by Western blot indicated that S. oralis, S. sanguis, A. viscosus, A. odontolyticus, and A. israelii contained TEPC-15-reactive antigens. The data show that many commonly occurring bacterial species found in dental plaque contain PC antigen and that immunization with plaque-derived PC antigens as a consequence of inflammation and periodontal attachment loss may influence systemic anti-PC antibody concentrations.

Actinomycetales↗

Antibody reactive with Porphyromonas gingivalis serotypes K1-6 in adult and generalized early-onset periodontitis.

BACKGROUND: Six serotypes of Porphyromonas gingivalis have recently been described. We sought to test the hypothesis that serotype specific carbohydrates from these strains are important antigens that elicit potent immune responses. METHODS: Serum concentrations of IgG reactive with P. gingivalis serotypes K1-K6 were determined for 28 adult (AP) and 28 generalized early-onset (G-EOP) periodontitis patients previously determined to be seropositive for a broken cell preparation of P. gingivalis. To confirm relationships suggested for K1, K2, and K6 in the analysis of initial data, the study population was increased to 133. RESULTS: Frequency of seropositivity for the 6 serotypes ranged from 26 to 54% of subjects. IgG concentrations ranged from 0 to 453 microg/ml with many subjects seropositive to more than one serotype. Concentrations for the subset of patients who was seropositive were high (mean responses ranged from 20 to 105 microg/ml for the 6 serotypes). Significant correlations between seropositivity to serotypes K1 and K5 as well as between K5 and K6 were found. CONCLUSIONS: We examined the relationship of diagnosis, race, gender, smoking, probing depth, attachment loss, and antibody reaction with the P. gingivalis serotypes by analysis of variance. Initial findings suggested potential relationships between diagnosis, smoking, race, gender, and antibody reactive with serotypes K1, K2, and K6. A significant relationship did exist between smoking and decreased antibody reactive with P. gingivalis serotype K2. No other relationships were substantiated. We also examined the IgG subclass distribution and found that responses were almost exclusively IgG2. These data support the concept that antibody responses to all 6 serotypes are common in both AP and G-EOP and that these K serotype carbohydrates elicit potent IgG2 responses.

Adult↗

Low-dose atropine in electroconvulsive therapy.

Anticholinergic medications such as atropine or glycopyrrolate have long been used in electroconvulsive therapy (ECT) to eliminate parasympathetically mediated dysrhythmias. However, such agents increase heart rate and myocardial workload and may increase risk of cardiac adverse events. What is needed is an intervention that is parasympatholytic without substantially increasing myocardial workload. In this study, a low dose of atropine was compared with placebo in ECT with attention to heart rate, blood pressure, cardiac rhythm, myocardial workload, and parasympathetic function. The dose of atropine that was used effectively blocked vagal tone with only a small and probably not clinically significant rise in myocardial workload for only a few minutes after the ECT seizure.

Adult↗

Health surveillance using an occupational medical database.

This pilot study sought associations between liver function tests (LFTs) and membership in homogeneous exposure groups (HEGs) at a target plant as pre-clinical indications of possible future occupational health problems. A large company database yielded linear models for each of six LFTs (total bilirubin, alkaline phosphatase, gammaglutamyl transferase, lactate dehydrogenase, aspartate transaminase, and alanine transaminase) in terms of sex, body mass index, age, race (white/non-white), alcohol and cigarette consumption, and production/non-production (P/NP) job, permitting control for these in analyses of LFTs vs HEGs at the plant. These analyses, with HEG substituted for P/NP in the large group model, resulted in loosely "suspect" associations significant at P < 0.10. Collapsed HEG variable (containing "suspects" separately and all other non-significant HEG levels pooled) yielded "confirmed suspects" at P < 0.05 in the analysis of an independent LFT set taken at the plant approximately one year later.

Data Interpretation, Statistical↗

Abbreviated cognitive test for delirium.

The cognitive test for delirium (CTD) was recently developed to identify delirium in an intensive care unit (ICU) setting. Stepwise discriminant analyses using the original validation sample indicated that a total score formed by summing only two of the nine content scores (visual attention span and recognition memory for pictures) maintained good reliability (coefficient alpha = 0.79) and the ability to discriminate delirium from dementia, schizophrenia, and depression (p < 0.0001) and delirium from moderate to severe dementia (p < 0.0002). This abbreviated version of the CTD is more practical for use by ICU clinicians.

Adult↗