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Biomedical subjects

A T Brown

Publications and source records attributed to A T Brown.

At least 19 recordsLinked to original sources

Oral Candida albicans in bone marrow transplant patients given chlorhexidine rinses: occurrence and susceptibilities to the agent.

The tongue and buccal mucosa of 26 bone marrow transplant recipients given three 0.12% chlorhexidine digluconate (CHX) oral rinses daily for 8 weeks were sampled weekly for oral Candida albicans. Putative C. albicans colony-forming units on selective bismuth sulfite glucose glycine yeast agar plates were identified with the API 20C system. The CHX minimum inhibitory concentrations (MICs) of oral C. albicans isolates obtained at all 8 sample weeks was determined with a microbroth dilution sensitivity assay. The CHX MIC range for yeast isolates selected randomly at all sample weeks was up to 2.5 to up to 20 micrograms/ml (mean MIC less than or equal to 8.5 micrograms/ml). The CHX MIC range for isolates at week 1 was less than or equal to 5 to less than or equal to 10 micrograms/ml (mean MIC less than or equal to 7.9 micrograms/ml) compared with less than or equal to 2.5 to less than or equal to 20 micrograms/ml at week 8 (mean MIC less than or equal to 8.8 micrograms/ml). Therefore the persistence of oral C. albicans in bone marrow transplant recipients using CHX rinses was due neither to low CHX susceptibilities nor to the development of resistance to the agent.

Bone Marrow Transplantation

Clinical and microbiological effects of a sanguinaria-containing mouthrinse and dentifrice with and without fluoride during 6 months of use.

The purpose of this study was to test the efficacy and safety of sanguinaria-containing regimens with and without fluoride using the American Dental Association guidelines for evaluating chemotherapeutic agents. The study was a 6-month, double-blind, 4-cell, placebo-controlled, parallel investigation involving 120 subjects. Following screening procedures, subjects were randomly assigned to 4 groups. Group 1 received a dentifrice containing 0.075% sanguinaria extract (SaE) and 2.0% zinc chloride (ZnCl2) in a dicalcium phosphate base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 2 received identical products without SaE or ZnCl2. Group 3 received a dentifrice containing 0.8% sodium monofluorophosphate, 0.075% SaE, and 0.05% ZnCl2 in a silica base, plus an oral rinse containing 0.03% SaE and 0.2% ZnCl2. Group 4 products were identical to those of Group 3 but without SaE and ZnCl2. Supragingival plaque and gingival inflammation were scored at 0, 1, 2, 1.5, 3, 4.5, and 6 months; bleeding upon probing was measured at 1, 1.5, 3, and 6 months. Microbiological samples were taken from plaque, tongue, and cheek areas. The active products produced statistically significantly lower scores than the placebo agents for all indices (P less than .0001). Six-month plaque scores were 13.1% lower for Group 1 and 17.4% lower for Group 3 compared to placebo products. When the Plaque Severity Index was applied, the percentage reductions were 33% for Group 1 and 41% for Group 3 compared to placebos. Gingival inflammation scores were 16.7% lower for Group 1 and 18.1% lower for Group 3 at 6 months compared to placebo scores.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

In vitro effect of chlorhexidine and amikacin on oral gram-negative bacilli from bone marrow transplant recipients.

Prophylactic use of chlorhexidine (CHX) mouthrinses has been shown to benefit the oral health status of bone marrow transplant recipients and other immunosuppressed persons and to reduce systemic complications of oral origin. However, a problem that often emerges with these patients is oropharyngeal and lower respiratory tract colonization by opportunistic aerobic or facultative gram-negative bacilli (GNB). Trends in four studies indicated that CHX rinses may predispose these persons to oral colonization by GNB such as the enterobacteria, Klebsiella pneumoniae and Enterobacter cloacae. Since GNB are generally susceptible to broad-spectrum aminoglycoside antibiotics such as amikacin, the in vitro sensitivities of K. pneumoniae, E. cloacae, Pseudomonas aeruginosa, and Escherichia coli ATCC reference strains and K. pneumoniae and E. cloacae oral clinical isolates to combinations of CHX and amikacin were determined by means of a disk diffusion sensitivity assay on Mueller-Hinton agar. The amikacin minimum inhibitory concentrations for all GNB tested were much lower (less than or equal to 4.69 to less than or equal to 9.37 micrograms/ml) than those for CHX (less than or equal to 18.75 to less than or equal to 300 micrograms/ml), and combinations of CHX and amikacin gave larger growth inhibition zones than CHX alone. No antibacterial antagonism between CHX and amikacin was found, and their solubilities were compatible. Therefore use of topical amikacin in conjunction with CHX rinses may reduce oral colonization by GNB in severely immunocompromised patient populations.

Amikacin

Chlorhexidine prophylaxis for chemotherapy- and radiotherapy-induced stomatitis: a randomized double-blind trial.

Patients receiving cytotoxic antineoplastic therapy often have treatment-associated stomatitis. A 0.12% chlorhexidine digluconate mouthrinse was evaluated (15 ml, three times a day) in a prospective, double-blind randomized trial as prophylaxis against cytotoxic therapy-induced damage to oral soft tissues. Seventy subjects, forty inpatients receiving high-dose chemotherapy and thirty outpatients receiving high-dose head and neck radiation therapy, were evaluated. Chlorhexidine mouthrinse significantly reduced the incidence of oral mucositis in the chemotherapy group on day 14 (p less than 0.02) and at 1 week follow-up on day 28 (p less than 0.002). Mucositis in the patients undergoing chemotherapy who received chlorhexidine also resolved more rapidly. Mucositis severity was significantly less compared to the control chemotherapy group on day 14 (p less than 0.03), day 21 (p less than 0.04), and on 1 week follow-up (p less than 0.02). Concomitant trends in the reduction in oral streptococci and yeast were noted in the chemotherapy group receiving chlorhexidine mouthrinse. Although no differences were observed in oral mucositis between the control and chlorhexidine groups of patients undergoing high-dose radiotherapy, similar reductions of oral microflora to those seen in the chemotherapy population were also noted for patients undergoing radiation therapy who received chlorhexidine. Although generally not significant, some increase in gram-negative bacilli was noted in the chlorhexidine-treated patients in both the chemotherapy and radiotherapy groups, but there was no correlation with increased systemic infection. Prophylactic chlorhexidine mouthrinse reduces oral mucositis and microbial burden in patients with cancer undergoing intensive chemotherapy.

Adult

Oral antimicrobial agents--chlorhexidine.

Chlorhexidine's structural characteristics give it potent antimicrobial activity, effectiveness at low concentrations, substantivity that prolongs its therapeutic effect in the oral environment, minimal resorption from the gastrointestinal tract, and the ability to reduce plaque. The use of this agent for oral stomatitis in neoplasia patients has recently been studied. Treatment-associated oral soft tissue inflammation and ulceration were significantly reduced by chlorhexidine in patients undergoing intensive chemotherapy. Reductions in total streptococci and yeast counts were also observed. When used in conjunction with systemic antifungal agents, such as nystatin or clotrimazole, a significantly decreased incidence of clinical oral candidiasis and Candida septicemia was observed. In contrast, in two studies in which high-dose head and neck radiation therapy was applied, there was no reduction in stomatitis. Oral gram-negative bacilli have been shown to increase in high-dose chemotherapy patients who are taking chlorhexidine during the treatment period (3 wk to 2 mo). However, no increase in systemic gram-negative infections or other adverse negative medical consequences were observed. This agent appears to be of therapeutic benefit in reduction of dental plaque, gingivitis, and stomatitis in the high-risk chemotherapy population when used in conjunction with other topical and systemic antimicrobial agents as prophylaxis. Although no toxic or serious adverse effects of chlorhexidine rinse have been observed in the short-term studies to date, the effects of longer-term chlorhexidine administration should be evaluated.

Bone Marrow Transplantation

Oral gram-negative bacilli in bone marrow transplant patients given chlorhexidine rinses.

Fifteen bone marrow transplant (BMT) patients who received three 0.12% chlorhexidine digluconate (CHX) mouthrinses daily for eight weeks were monitored weekly for the occurrence of oral opportunistic Gram-negative bacilli (GNB). Tongue and buccal mucosa were sampled with use of Culturette swabs that were streaked on plates containing selective MacConkey agar. After incubation, colony-forming units were scored and putative GNB classified with use of the API 20E rapid identification system and supplemental biochemical tests. After identification, the susceptibilities of all GNB to CHX were determined by means of a disk diffusion sensitivity assay. Sixty-seven percent (10) of the BMT subjects had at least one GNB-positive tongue culture, and 53% (8) had GNB in samples taken from the buccal mucosa. Of 218 samples taken, 26% and 24% from the tongue and buccal mucosa, respectively, were GNB-positive. The predominant clinical GNB isolates were Enterobacter cloacae (46%) and Klebsiella pneumoniac (30%). Their respective CHX minimum inhibitory concentrations (MICs) were similar to those of ATCC reference strains. Although the CHX MIC values of the clinical GNB isolates were high (less than or equal to 37.5 to less than or equal to 300 micrograms/mL), they were not dependent upon length of exposure to the agent. Therefore, changes in sensitivity or resistance to CHX did not appear to occur. The results suggest that the mouths of BMT patients--and perhaps of other immunosuppressed individuals--should be routinely monitored for GNB, as are other clinically important sites, such as the throat and the urinary and gastro-intestinal tracts.

Adolescent

Coordinate decrease of tissue insulinlike growth factor I posttranscriptional alternative mRNA transcripts in diabetes mellitus.

In these studies, we examined the effect of excess levels of growth hormone (GH) on rat insulinlike growth factor I (IGF-I) gene expression in streptozocin-induced diabetes mellitus. A solution hybridization/RNase protection assay was used to simultaneously quantitate the relative tissue content of the variant IGF-I mRNA species arising from alternative splicing in the region encoding the COOH-terminal extension E-peptide (IGF-Ia and IGF-Ib). IGF-Ia and IGF-Ib mRNAs were markedly decreased in liver, kidney, and lung tissues of diabetic rats. Although GF stimulates IGF-I gene expression, chronic GH excess from implanted somatomammotropic tumors did not appropriately induce tissue IGF-I mRNA content in diabetic animals. Treatment of diabetic rats with insulin for 1 wk restored basal and GH-stimulated IGF-Ia and IGF-Ib mRNA content toward that present in tissues of nondiabetic rats. The ratio of IGF-Ia to IGF-Ib mRNA remained relatively constant for each tissue and was not affected by the diabetic state, chronic GH hyperstimulation, or insulin therapy, suggesting that posttranscriptional splicing is not a regulated event in these conditions. Thus, both circulating IGF-I levels and tissue IGF-I gene expression are profoundly decreased in this model of experimental diabetes. Diminished tissue availability of IGF-I from endocrine and/or paracrine sources may be responsible for the growth retardation seen in uncontrolled diabetes mellitus.

Animals

Control of oral mucositis and candidiasis in marrow transplantation: a prospective, double-blind trial of chlorhexidine digluconate oral rinse.

Conditioning chemoradiotherapy damages the mucosal barrier of the mouth and throat and often produces severe oral inflammation and infection. In a prospective, double-blind, randomized study, we examined the use of a chlorhexidine digluconate mouthrinse for prophylaxis against oral mucosal complications in 51 bone marrow transplant patients. Use of chlorhexidine mouthrinse produced significant reductions in the incidence and severity of oral mucositis. Mucositis also resolved more quickly in patients receiving chlorhexidine. Concomitant reductions in total oral streptococci (p less than 0.02-p less than 0.001) and oral candida (p less than 0.004) were seen in patients using chlorhexidine. Persistent clinical oral candidiasis (thrush) was observed in 15 to 27 control group patients (56%), but only transiently in two (8%) of 24 patients who used chlorhexidine rinse (p less than 0.001). Five of 27 control group patients (19%) had candidemia, while no candidemia was observed in the chlorhexidine group (p less than 0.03). Three deaths from disseminated candidiasis occurred in the placebo group; none occurred in patients who received chlorhexidine. Prophylactic use of chlorhexidine mouthrinse produces reductions in oral soft tissue disease and oral microbial burden in patients undergoing bone marrow transplantation. The reductions in mucositis and in oral candida infections observed with prophylactic chlorhexidine mouthrinse represent a significant advantage for patients undergoing marrow transplantation.

Adolescent

Therapeutic use of chlorhexidine in bone marrow transplant patients: case studies.

Patients undergoing cytotoxic chemotherapy and radiation therapy often experience severe oral complications during and after treatment despite supervised oral hygiene and conventional antimicrobial regimens. The antimicrobial compound chlorhexidine is an effective topical prophylactic agent against oral mucositis and candidiasis. Oral mucositis developed in four patients who underwent bone marrow transplantation; the condition was severe enough to prompt use of chlorhexidine. In each case, there was clinical resolution of mucositis and a concomitant decrease in the oral microbial burden 1 week after chlorhexidine use began. This strongly suggests that, in addition to its value in protecting these severely immunocompromised patients from oral infection, chlorhexidine also offers a therapeutic benefit in the resolution of existing oral infections and of mucositis.

Adult

Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants.

Intensive chemoradiotherapy damages the mucosal barrier of the mouth and throat and is often associated with severe oral inflammation and infection. This study examined the use of a 0.12% chlorhexidine gluconate mouthrinse for prophylaxis against oral complications in patients receiving bone marrow transplants. Use of chlorhexidine mouthrinse produced reductions in oral soft tissue disease and oral microbial burden, including a significant decrease in oral mucositis and Candida infections. The advantage for patients undergoing intensive antineoplastic therapy, and potentially for other immunocompromised patients susceptible to oral infections, was studied.

Adolescent

Comparison of two screening tests for Streptococcus mutans and evaluation of their suitability for mass screenings and private practice.

Two simple microbiological tests for quantitating salivary Streptococcus mutans levels were compared with each other and evaluated for suitability for mass screenings and private practice. Both tests use mitis salivarius medium with bacitracin (MSB) and are selective for S. mutans. One test estimates colonies grown on agar (MSBA) and the other estimates colonies grown in broth that adhere to glass (MSBB). Both are scored from 1 (lowest) to 5 (highest). Children (293) in grades 5 and 6 in Tallahassee, Florida (nonfluoridated) were tested for S. mutans levels. Scores of children by both tests were significantly similar (chi 2, regression and Kappa statistical analysis). Correlation coefficients (regression) between scores and DMFS increments of the previous 4 yr were 0.35 (MSBA) and 0.26 (MSBB). Both tests were very good in identifying children with low caries increments, but positive scores did not correlate well with high caries increments. Sampling and interpreting took 2 min (MSBA) and 1 min (MSBB). Cost of MSBA/child was $1.15, and MSBB/child $1.25. These tests are economical and suitable for mass screenings to identify low risk populations who do not require preventive treatment.

Bacteriological Techniques

Ammonia utilization by a proposed bacterial pathogen in human periodontal disease, Capnocytophaga ochracea.

Capnocytophaga ochracea strain 25 was originally isolated from a patient with severe juvenile periodontitis. An NAD-specific glutamate dehydrogenase (GDH) (EC 1.4.1.2.) was found in cell-free extracts from this organism. The NADH-dependent reductive, or ammonia-assimilating activity (NADH-GDH), of the enzyme was 8-10-fold higher than its NAD-dependent oxidative, or ammonia-releasing activity (NAD-GDH), suggesting that the primary physiological role of the GDH is ammonia-fixing. Capnocytophaga ochracea GDH was purified approximately 39-fold by a rapid, single-step purification procedure using DEAE-cellulose (DE52) ion-exchange column chromatography which gave 90 per cent recovery of total enzyme units. Paper chromatography of an NADH-GDH assay mixture containing the partially purified enzyme showed that glutamate was, indeed, a product of the ammonia-assimilating reaction. The pH optimum for the NAD-GDH reaction was 9.0; that for the NADH-GDH reaction was 7.5. Although a number of mono- and divalent cations were tested, none had a large effect on either NAD-GDH or NADH-GDH activity. The NAD-GDH reaction showed a hyperbolic kinetic response to glutamate and NAD and the Km values for glutamate and NAD were 2.44 and 0.083 mM respectively. The kinetic response of the NADH-GDH reaction to NADH, alpha-ketoglutarate and ammonium chloride also obeyed Michaelis-Menten kinetics and their respective Km values were 0.069, 1.44 and 3.33 mM. Of a number of biologically-active compounds tested for their ability to modulate GDH activity, only ADP and NAD exerted much effect. The NADH-GDH activity showed a negative hyperbolic kinetic response to both ADP and NAD and Dixon plot-analysis of the NAD and ADP saturation data gave Ki values for ADP and NAD of 4.0 and 0.46 mM respectively. Both NAD and ADP appeared to exert their negative effects on NADH-GDH activity by completely inhibiting the binding of the reduced coenzyme, NADH, to the enzyme.

Ammonia

A case study of a nontraditional basic science curriculum.

This article presents a critical analysis of the ten-year experience of the Department of Oral Biology of the University of Kentucky College of Dentistry with a nontraditional basic science curriculum. The factors that led to the adoption of this curriculum are outlined, and its effects on students, faculty, and the college's administration are described. The pitfalls inherent in this approach and in the individualized self-instructional format for teaching the basic sciences to dental students are discussed. This critical evaluation is aimed at providing information for those contemplating similar sweeping curricular changes in the future to enable them to make rational decisions and to help them predict the effects of such changes on the educational program.

Curriculum