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Biomedical subjects

Anthony J Smith

Publications and source records attributed to Anthony J Smith.

At least 37 records · Page 2Linked to original sources
PubMed2003

Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity.

AIMS: To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS: All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay (LOS) and intensive care (ICU) admission rate were extracted from a standardized, prospectively collected database. Comparisons were made between moclobemide alone and moclobemide with a serotonergic coingestant poisoning. Serotonin toxicity was defined by a combination of Sternbach's criteria and a clinical toxicologist's diagnosis. In five patients serial moclobemide concentrations were measured. Time to maximal plasma concentration (Tmax), peak plasma concentration (Cmax) and terminal elimination half-lives were estimated. RESULTS: Of 106 included patients, 33 ingested moclobemide alone, 21 ingested moclobemide with another serotonergic agent (in some cases in therapeutic doses) and 52 ingested moclobemide with a nonserotonergic agent. Eleven (55%) of 21 patients coingesting a serotonergic drug developed serotonin toxicity, which was significantly more than one (3%) of 33 moclobemide-alone overdoses (odds ratio 35, 95% confidence interval 4, 307; P < 0.0001). In six of these 21 cases severe serotonin toxicity developed with temperature >38.5 degrees C and muscle rigidity requiring intubation and paralysis. The 21 patients had a significantly increased LOS (34 h) compared with moclobemide alone overdoses (12 h) (P < 0.0001) and a significantly increased ICU admission rate of 57% vs. 3% (P < 0.0001). Time to peak plasma concentration was delayed in two patients where prepeak samples were obtained. Cmax increased slightly with dose, but all three patients ingesting > or = 6 g vomited or had charcoal. The mean elimination half-life of moclobemide in the five patients in whom serial moclobemide concentrations were measured was 6.3 h and elimination was first order in all cases. There was no evidence of a dose-dependent increase in half-life. CONCLUSIONS: The effects of moclobemide alone in overdose are minor, even with massive ingestions. However, moclobemide overdose in combination with a serotonergic agent (even in normal therapeutic doses) can cause severe serotonin toxicity. The elimination half-life is prolonged by two to four times in overdose, compared with that found in healthy volunteers given therapeutic doses. This may be a result of wide interindividual variation in overall elimination, also seen with therapeutic doses, but appears not to be due to saturation of normal elimination pathways.

Adult↗
PubMed2003

Identification of hierarchical factors to guide clinical decision making for successful long-term pulp capping.

OBJECTIVE: Clinicians have few quantitative studies that rank the in vivo pulp capping effects of commonly used restorative materials. These factors were investigated to provide guidance to clinicians. METHOD AND MATERIALS: One hundred sixty-one standardized pulp-exposed cavities were prepared in nonhuman primate teeth. Exposed pulps were capped with calcium hydroxide, resin-modified glass-ionomer cements, and resin composites. Teeth were collected from 7 to 720 days to observe a full range of responses. Pulpal reactions were categorized according to the standards set by the International Standards Organization. Bacteria were detected with McKay's stain. RESULTS: The incidence of bacterial microleakage was 19.7% with resin composite, 21.1% with resin-modified glass-ionomer cement, and 47.0% with calcium hydroxide. The severity of pulpal inflammation increased with the presence of bacteria or tunnel defects. The severity of pulpal inflammation prevented dentinal bridge formation at varying levels: slight for resin composite and resin-modified glass-ionomer cement, and severe with calcium hydroxide. The incidence of severe inflammation or pulpal necrosis was 7.9% with resin composite, 10.6% with calcium hydroxide, and 10.5% with resin-modified glass-ionomer cement. Other variables, such as pulpal exposure width and tertiary dentin formation, were not highly correlated to pulpal inflammation. CONCLUSION: Pulp capping with resin composite provided the lowest incidence of bacterial microleakage, the lowest levels of pulpal inflammation, and the lowest incidence of necrosis.

Analysis of Variance↗
PubMed2003

Vitality of the dentin-pulp complex in health and disease: growth factors as key mediators.

The vitality of the dentin-pulp complex, both during tissue homeostasis and after injury, is dependent on pulp cell activity and the signalling processes, which regulate the behavior of these cells. Research, particularly over the last ten to fifteen years, has led to a better understanding of the molecular control of cellular behavior. Growth factors play a pivotal role in signalling the events of tissue formation and repair in the dentin-pulp complex. Sequestration of growth factors in the dentin matrix during tissue formation provides a pool of these molecules, which may be released during injury and contribute to signalling of reparative events. Therapeutic intervention with recombinant growth factors also provides possibilities for control of cell activity during repair. Harnessing both endogenous and exogenous sources of growth factors can provide exciting opportunities for novel biological approaches to dental tissue repair and the blueprint for tissue engineering of the tooth. These approaches offer significant potential for improved clinical management of dental disease and maintenance of tooth vitality.

Dental Pulp↗
PubMed2002

Limitations of Health Insurance Commission (HIC) data for deriving prescribing indicators.

OBJECTIVES: To derive indicators of quality prescribing by Australian general practitioners based on Health Insurance Commission (HIC) data and assess the influence of incomplete capture of data on under-copayment drugs on the validity of these indicators. DESIGN: Two expert groups proposed prescribing indicators that can be derived from aggregate prescribing data, and which reflect important clinical or cost-effectiveness issues. Indicators were examined using HIC data and compared with national prescribing trends over time using Australian Statistics on Medicines. The effect of incomplete data capture on indicator interpretation was examined by stratifying GPs into five strata based on the proportion of concession card holders in their practice. PARTICIPANTS: Approximately 14,000 Australian GPs providing > or = 1500 Medicare services per year. MAIN OUTCOME MEASURES: Measures of prescribing for individual GPs (based on HIC data 1993-1997). RESULTS: Forty-three potentially useful indicators were identified. These covered a fairly narrow range of prescribing activities and many required additional clinical information for interpretation. Indicators based on prescribing rates gave a misleading picture of prescribing trends where the extent of HIC data capture changed over time. Indicators expressed as ratios that reflected choice of agent within a drug class were less affected by incomplete data capture. CONCLUSIONS: Indicators of quality prescribing can be derived from HIC data. However, indicators for under-copayment drugs that represent prescribing rates may unfairly classify doctors practising in areas of socioeconomic disadvantage or high morbidity as "high prescribers". Ratio indicators are more robust, and may be more valid prescribing measures. If HIC data are to be used to monitor the quality of prescribing, data on all prescriptions dispensed will be needed.

Australia↗
PubMed2002

Bacterial microleakage and pulp inflammation associated with various restorative materials.

OBJECTIVES: Many restorative materials are claimed to be successful in preventing bacterial microleakage and minimizing pulp inflammation. However, information regarding the in vivo performance of materials in comparison with each other is limited. The aim of this study was to evaluate and compare the pulp response of nine restorative materials when placed in non-exposed monkey cavities. METHODS: 279 standardized non-exposed Class V cavities, were prepared into buccal dentin. Cavities were restored with a number of materials in the following categories: Zinc oxide eugenol (ZnOE), Calcium hydroxide [Ca(OH)(2)], zinc phosphate (ZP), Resin-modified glass ionomer (RMGI), Composite resin (CR), Bonded amalgam (BA), Gutta-percha (GP), Compomer and Silicate. Pulp tissues were collected and evaluated at short, intermediate and long-term intervals according to ISO guidelines; employing histomorphometric analysis, Spearman's rho and ANOVA statistics. Pulp responses were categorized according to FDI, ISO and ADA standards. Bacteria were detected using McKay stains. RESULTS: Pulp inflammation was found to be correlated to bacterial microleakage around the restoration (p < or =0.0001). The frequency of bacterial microleakage was found to vary between restorative materials (p < or =0.0001). In rank order of preventing bacterial microleakage from best to the worst; RMGI (100%), BA (88%), ZnOE (86%), CR (80%), GP (64%), Ca(OH)(2) (58%), compomer (42%), silicate (36%) and ZP (0%). SIGNIFICANCE: The most effective restorative materials to prevent bacterial microleakage and pulp injury from inflammatory activity were RMGI, BA, ZnOE and CR restorations.

Analysis of Variance↗
PubMed2002

The effect of etching on bacterial microleakage of an adhesive composite restoration.

OBJECTIVES: The incidence of bacterial microleakage, pulp inflammation and necrosis associated with dentine etching treatments prior to restoration are not known. Consequently, to resolve some of the controversy surrounding the effects and importance of vital dentine etching, the authors investigated these factors. METHODS: 110 standardised class V cavities were cut into buccal dentine, without exposing the pulp of teeth scheduled for extraction for orthodontic reasons. Cavities were either left unetched, or etched with the non-equivalent treatments of phosphoric acid gel for 60s or Ethylenediaminetetraacetic acid (EDTA) for 30s, prior to placement of composite resin. Teeth were collected and pulp responses were evaluated according to ISO guidelines, using pathohistomorphometric analysis and ANOVA statistics. RESULTS: Etching was found to be correlated to bacterial microleakage (p=0.0001) and tertiary dentine formation (p=0.0023). Bacterial microleakage was correlated to inflammatory activity (p=0.0001). The frequency of bacterial microleakage was: no etching (65%), EDTA (51%) and phosphoric acid (PA) (20%). SIGNIFICANCE: Vital dentine etching treatment is of extreme importance for the placement of RC to minimise bacterial microleakage. PA etching proved to be more effective at preventing bacterial microleakage than non-etching, and etching with EDTA.

Acid Etching, Dental↗
PubMed2002

Age-related odontometric changes of human teeth.

OBJECTIVE: The number of older patients requiring restorative treatment are likely to increase due to improvements in oral health and increased longevity. However, aging odontometric data are lacking. The aim of this study was to determine possible changes in pulp cell density, pulp area, and dentinal thickness with age. STUDY DESIGN: Incisors (50), canines (39), premolars (51), and molars (7) extracted from 60 patients aged between 10 and 59 years, were analyzed histomorphometrically for cell density (odontoblasts, subodontoblasts, and pulp core fibroblasts) and dentinal thickness. RESULTS: With increasing patient age, in both crown and root aspects of teeth, dentinal thickness increased (P <.001), while the density of odontoblasts (P <.001), subodontoblasts (P = 0.001), and pulp fibroblasts (crown, P <.011; root, P =.0015) decreased. The degree of age-related changes in teeth appeared to be asymmetrical, with decreases in the root being greater than in the crown. At all ages pulp cell densities, including odontoblasts, within the crown were greater than in the root (P <.001), even though the calculated rate of dentinal deposition was greatest in the root. CONCLUSION: Decreases in pulp cell density may reduce pulp repair activity after restorative treatments, although increases in dentinal thickness may aid pulp protection. An understanding of these age-related changes will influence the provision of restorative and endodontic care and benefit older patients.

Adolescent↗
PubMed2002

Preserving the vital pulp in operative dentistry: I. A biological approach.

This is the first in a series of four papers aimed at understanding human pulpal responses to tissue injury, cavity preparation and restorative events. This article provides an insight into the exquisite regenerative potential of the dentine-pulp complex which underpins the success of restorative dentistry.

Acid Etching, Dental↗
PubMed2002

Preserving the vital pulp in operative dentistry: 2. Guidelines for successful restoration of unexposed dentinal lesions.

The exciting treatment possibilities arising from tissue engineering approaches are still some years away from involvement in dentistry. Meanwhile, it is important to optimize conventional treatments, although precise information on pulp responses to cavity preparation and restoration variables are limited. Odontoblast survival, pulp inflammation, and tertiary dentine area are used as measures of pulp injury and repair.

Analysis of Variance↗
PubMed2002

Preserving the vital pulp in operative dentistry: 3. Thickness of remaining cavity dentine as a key mediator of pulpal injury and repair responses.

Confusion surrounds the pivotal role played by the remaining dentine thickness in a cavity in determining pulpal injury and repair response outcomes after restorative treatment. The multifactorial nature of the injury repair response requires that attention is focused on the most important factors, including remaining dentine thickness, to harness the natural regenerative properties of the pulp and to avoid postoperative treatment complications.

Cell Count↗
PubMed2002

Saving pulps--a biological basis. An overview.

AIM: Cavity preparation and restoration variables have an uncertain relationship to pulp injury and repair responses. The purpose of this paper is to determine the importance of cavity preparation and restoration variables, by ranking them according to their effect on pulp injury (odontoblast survival) and pulp repair (reactionary dentine secretion). METHOD: The seven studies reviewed are all based on the protocols described by Murray, Smith and colleagues in 2000 and 2001. RESULTS: The studies reviewed provide new perspectives on the importance of cavity preparation and restoration variables in mediating pulp activity. CONCLUSIONS: The onset of post-operative complications may be most productively minimised by focusing practitioner attention to aspects of treatment highlighted in this review.

Adolescent↗
PubMed2002

Cavity remaining dentin thickness and pulpal activity.

PURPOSE: To investigate pulpal injury by measuring odontoblast numbers, and pulp dentin repair activity by measuring reactionary dentin area, in relation to the remaining dentin thickness (RDT) of cavity preparations in 217 human teeth. MATERIALS AND METHODS: Cavities were restored with adhesive bonded composite, resin-modified glass-ionomer cement, zinc oxide-eugenol or calcium hydroxide materials. The teeth were extracted for orthodontic reasons between 20-381 days post-operatively, and odontoblast numbers and reactionary dentin area were analyzed histomorphometrically, and statistically using ANOVA. RESULTS: Reactionary dentin deposition was observed beneath cavities with a RDT above 0.5 mm as well as beneath cavities with a RDT below 0.25 mm; however maximal reactionary dentin appeared to be beneath cavities with an a RDT between 0.5-0.25 mm (P= 0.0001). The area of reactionary repair was also influenced by the choice of restoration material (P= 0.0385) from greatest to least; calcium hydroxide, composite, resin-modified glass-ionomer cement and zinc oxide-eugenol. Odontoblast numbers were maintained beneath cavities with a RDT above 0.25 mm, cavities placed closer to the pulp appeared to injure underlying odontoblasts, reducing their numbers (P= 0.0001). The choice of cavity restoration material also influenced the survival of underlying odontoblasts (P= 0.0061).

Acid Etching, Dental↗
PubMed2002

Histomorphometric analysis of dentinal bridge formation and pulpal inflammation.

OBJECTIVE: The purpose of this study was to evaluate pulpal responses to the use of four resin composite materials as direct pulp capping agents. The importance and effects of individual pulp capping variables are not well understood; consequently histomorphometric analysis was used to analyze these variables. METHOD AND MATERIALS: Two hundred fifty standardized pulp-exposed cavities were prepared in nonhuman primate teeth. Exposed pulps were capped with calcium hydroxide and multistep and self-etching primer resin composites. Teeth were collected from 3 to 60 days to observe pulpal reactions. Following perfusion fixation, tissues were demineralized, sectioned, stained, and histomorphometrically measured. Bridge area, diameter of pulpal exposure, and cavity floor width were measured. Tunnel defects, operative debris, and pulpal inflammation were graded according to defined criteria. RESULTS: The variables correlated to dentinal bridge area were, in decreasing order of significance, time elapsed since exposure, diameter of pulpal exposure, pulp capping material, and tunnel defects. The variables correlated to pulpal inflammation were the type and curing of pulp capping material. Other variables were not statistically significant. CONCLUSION: Pulp capping with resin composite materials provided acceptable pulpal inflammatory and dentinal bridge repair responses, comparable with those of calcium hydroxide. Although resin composites are promising as direct pulp capping agents, further investigations are required to optimize their application protocols to reduce the penetration of potentially cytotoxic monomers into pulpal tissue.

Acid Etching, Dental↗
PubMed2002

Hierarchy of pulp capping and repair activities responsible for dentin bridge formation.

PURPOSE: The importance of pulp capping variables which mediate pulp repair activities and dentin bridge formation following pulp exposure are not well understood. Consequently, the aim of this study was to investigate the effects of pulp capping variables on tertiary dentin bridge formation. MATERIALS AND METHODS: Calcium hydroxide [Ca(OH)2], resin-modified glass-ionomer (RMGI) and resin-based composite (RBC) were used to restore pulp exposures prepared in 161 nonhuman primate teeth, according to ISO usage guidelines. Teeth were collected from between 7 and 720 days to observe the pulp repair activities leading to dentin bridge formation. Bacteria were detected using McKays stain. Pulp activity was categorized histomorphometrically using ISO standards, and analyzed statistically using ANOVA statistics. RESULTS: The pulp capping variables in order of their relationship to dentin bridge area, from the most important to the least important were: time elapsed since pulp capping (P = 0.0009), pulp capping materials (P = 0.0252), bacterial microleakage (P = 0.0358) and area of operative debris in the dentin bridge (0.0362). A further 10 pulp capping variables were found to be less important. Relationships between pulp capping materials, operative debris, tunnel defects, bacterial microleakage, inflammation and dentin bridge formation were observed. Bacteria contaminated 18.6% of RBC, 22.2% of RMGI and 47.0% of Ca(OH)2 capped pulps.

Analysis of Variance↗
PubMed2002

Paraproteins: a regional South Australian experience.

We have performed a systematic review of all new serum and urinary paraproteins detected over a six year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses and associated laboratory features were ascertained from a computerized laboratory database or from clinical notes. Over the period of study, serum or urine paraproteins were detected in 613 new patients. These consisted of 568 patients with serum paraproteins and 45 patients with urinary monoclonal free light chain (in the absence of a serum paraprotein). These paraproteins occurred more commonly in males and the frequency increased with age. Approximately 30% of the serum paraproteins and 60% of urinary monoclonal free light chain were associated with B cell lymphoproliferative disorders (multiple myeloma, plasmacytoma, Waldenstrom's macroglobulinemia, non-Hodgkins lymphoma, chronic lymphocytic leukemia, etc) with the remainder being labeled as monoclonal gammopathies of uncertain significance (MGUS). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of paraprotein, B2 microglobulin, the presence of free urinary light chain and demonstrated molecular size heterogeneity of the paraprotein but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients. In conclusion paraproteins were most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of serum paraprotein (> 15 g/l), elevated levels of B2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen with patients with MGUS, regular monitoring of paraprotein level is considered mandatory in the management of these patients.

Adult↗