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Biomedical subjects

D J White

Publications and source records attributed to D J White.

At least 163 records · Page 9Linked to original sources
PubMed1995

Postburn cardiac contractile function and biochemical markers of postburn cardiac injury.

BACKGROUND: In vivo assessment of cardiac injury and contractile deficits after thermal injury remain difficult as neurohumoral compensatory mechanisms maintain cardiac output. While measurement of creatine kinase (CK) and the isoenzyme of creatine kinase (CKMB) have been used as clinical indicators of cardiac injury, these biochemical markers are not completely specific for cardiac muscle. Cardiac protein troponin I (cTnI) is unique to the myocardium but can be detected in the systemic circulation within three to four hours after cardiac injury. The purpose of this study was to examine cardiac contractile function at several postburn intervals and to correlate the appearance of cardiac dysfunction with biochemical measures of cardiac injury (serum concentration of CK, CKMB, and cTnI). STUDY DESIGN: New Zealand white rabbits were deeply anesthetized and a scald burn comprising 34 percent of the total body surface area (n = 36) or sham burn (n = 36) was accomplished using a template device. All burn rabbits were given lactated Ringer's solution (4 mL/kg/percent burn, Parkland formula). Blood samples were collected immediately prior to sacrifice in six animals from both burn and control groups, and animals were sacrificed either two, four, six or 24 hours after burn. Cardiac function was assessed in left ventricular preparations (Langendorff) and serum CK, CKMB, and cTnI levels were determined. RESULTS: Cardiac dysfunction occurred at all times after burn as indicated by a lower peak systolic left ventricular pressure and +/- dP/dt maximum compared with time-matched shams and the shift of left ventricular function curves plotted for burn groups downward and to the right of those calculated for shams, p < 0.05. Left ventricular systolic dysfunction after burn correlated with a progressive rise in cTnI and CK but not CKMB. CONCLUSIONS: The cardiospecificity of the cTnI eliminates concerns about tissue source associated with CK and CKMB and provides a biochemical measure of cardiac injury that is consistent with in vitro assessment of cardiac dysfunction.

Animals↗
PubMed1995

Role of xanthine oxidase and leukocytes in postburn cardiac dysfunction.

BACKGROUND: Recent studies suggest that the cardiac dysfunction that occurs after a major burn is mediated by oxygen-derived free radicals. This hypothesis is based on the fact that superoxide dismutase and catalase, given with fluid resuscitation from burn injury, provided significant cardioprotection. STUDY DESIGN: In this present study, rats received either enteral allopurinol or tungsten-enriched diets to determine if xanthine oxidase mediates postburn defects in cardiac contraction and relaxation. Polymorphonuclear neutrophil (PMN) were depleted to examine the contribution of PMN-derived factors to postburn cardiac dysfunction. Rats were divided into eight groups: groups 1 to 6 received regular chow, and groups 7 and 8 received tungsten-enriched diets for 14 days before study. Groups 2, 4, 6, and 8 were given a third-degree burn comprising 43 +/- 2 percent total body surface area and were resuscitated with Ringer's lactated solution for 24 hours (4 mL/kg/percent burn). In group 2, burned rats received fluid resuscitation alone; in group 4 (n = 10), rats were given allopurinol, 10 mg/kg daily by gastric lavage for five days preburn, group 6 (n = 11) received vinblastine (0.75 mg/kg) four days preburn, and group 8 (n = 11) received tungsten-enriched diets for 14 days before burn; sham burn controls included vehicle-treated (n = 10), allopurinol-treated (n = 8), PMN-depleted (n = 8), and tungsten-fed rats (n = 11) (groups 1, 3, 5, and 7, respectively). RESULTS: Burn injury produced mild hypotension, hypothermia, bradycardia, and a significant decrease in left ventricular performance, despite aggressive fluid resuscitation (group 2). Allopurinol, tungsten-enriched diets, and PMN depletion partially attenuated burn-induced cardiac contractile dysfunction and improved left ventricular responsiveness to increases in preload, coronary flow rate and exogenous calcium. CONCLUSIONS: Our data suggest that xanthine oxidase-derived oxygen metabolites and PMN-derived mediators contribute to postburn cardiac contractile deficits.

Allopurinol↗
PubMed1995

A new Plaque Glycolysis and Regrowth Method (PGRM) for the in vivo determination of antimicrobial dentifrice/rinse efficacy towards the inhibition of plaque growth and metabolism--method development, validation and initial activity screens.

A new method, the Plaque Glycolysis and Regrowth Method (PGRM), is described for the evaluation of antimicrobial effects on plaque metabolism in vivo. The method relies on the experimental observation that in vivo sampled dental plaques, collected from different quadrants of the dentition, produce equivalent rates of metabolic activity and regrowth when similarly dispersed and normalized into incubation media. In applications of the technique to antimicrobial evaluations, overnight fasted dental plaque is collected from a non-treated quadrant of the dentition along the gingival margin. Topical formulations are used in vivo. Following this, dental plaques are collected from other dentition quadrants at extended times, allowing for the back diffusion, clearance and natural intraoral deactivation of antimicrobials within the oral cavity. In vivo treated and non-treated plaque samples are subsequently tested for metabolic and regrowth activity under controlled and standardized conditions in vitro following normalization for biomass. The technique thus combines the necessary biological factors important to the legitimate evaluation of antimicrobial effects in vivo, while benefiting from the improved precision and control provided by in vitro assessment of plaque activity. In this paper evidence is presented validating the PGRM method, and initial activity screens of commercial antimicrobial mouthrinses and toothpastes, including a new stabilized stannous fluoride dentifrice, are described.

Analysis of Variance↗
PubMed1995

Effects of nine weeks' use of a new stabilized stannous fluoride dentifrice on intrinsic plaque virulence expressed as acidogenicity and regrowth: a modified PGRM study.

A new stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care has been examined for its effects on intrinsic plaque metabolic and regrowth activity and effects on plaque resistance to SnF2 throughout nine weeks of toothbrushing. Subjects brushed their teeth 1 X, 2 X or 3 X/day with stabilized stannous fluoride dentifrice or placebo dentifrice for nine weeks, presenting in the morning on weeks 3, 6-9 for plaque sampling. Following nine weeks, subjects were crossed-over and repeated the experiment on their alternative assigned product (active SnF2/placebo). Sampled dental plaques were evaluated for standardized glycolysis and regrowth activity using the "Plaque Glycolysis and Regrowth Method" (PGRM). Following the second nine-week treatment period, subjects concluding either placebo or SnF2 toothbrushing participated in a single-treatment PGRM experiment using stabilized stannous fluoride dentifrice. Toothbrushing with stabilized stannous fluoride dentifrice in this experiment produced significant and sustained reductions in both plaque glycolytic and regrowth activity as compared to placebo treated plaques. In the concluding single-brushing PGRM experiment, SnF2 dentifrice was shown to produce equal inhibitory actions in plaque from subjects completing stannous fluoride or placebo treatments. This result confirmed that nine weeks toothbrushing with stabilized stannous fluoride dentifrice produced no development or resistance of plaque to SnF2 inhibition. These results support the strong in vivo antimicrobial actions of the stabilized stannous fluoride dentifrice, Crest Gum Care.

Analysis of Variance↗
PubMed1995

Antimicrobial effects of a stabilized stannous fluoride dentifrice in reducing plaque acid production--a single-brushing PGRM study.

A Plaque Glycolysis and Regrowth Method (PGRM) has been used to evaluate the in vivo antimicrobial activity of a new stabilized stannous fluoride dentifrice in comparison to a control dentifrice (Regular Crest, containing NaF) and a second commercial dentifrice containing SnF2. In the method, plaque collected from subjects prior to toothbrushing served as control for subsequent plaque samples collected following toothbrushing with assigned formulations. Inhibition of plaque metabolic activity was determined by the comparative acidogenicity of normalized plaque samples as contrasted with control plaques incubated similarly. Results from a sixteen-person cross-over study demonstrated that the improved stabilized stannous fluoride dentifrice significantly reduced plaque metabolism of sucrose in comparison to both placebo and commercial SnF2 dentifrice formulations following a single toothbrushing with 2.5 grams of dentifrice for over 90 minutes following treatment. These results support the strong antimicrobial activity of the stabilized stannous fluoride dentifrice, currently marketed as Crest Gum Care, in inhibiting plaque metabolism/acid production following in vivo toothbrushing.

Analysis of Variance↗
PubMed1995

Effect of a stabilized stannous fluoride dentifrice on plaque acid (toxin) production.

A Plaque Glycolysis and Regrowth Method (PGRM) has been used to examine the effects of single brushing with a new stabilized stannous fluoride dentifrice on plaque acid production. Plaque samples collected 45 minutes after subject toothbrushing were compared with samples collected prior to toothbrushing for glycolytic activity (pH reduction in incubation media), and the composition and proportion of acids produced during metabolism (capillary electrophoresis). Subjects brushed with both active SnF2 and placebo dentifrices in a cross-over design. Acetic and lactic acid were found to be produced during PGRM metabolism. SnF2 dentifrice was observed to significantly inhibit plaque glycolysis, reducing the pH drop associated with acid production. and specifically inhibiting both lactic acid and acetic acid production. Control dentifrice had a modest inhibitory effect on acid production, primarily inhibiting acetic acid production. SnF2 dentifrice inhibited lactic acid production more effectively than control dentifrice, and this effect appeared to be related to SnF2 specificity in metabolic inhibition, as opposed to the components of control dentifrice, namely ionic fluoride and surfactant. These experimental results support the in vivo antimicrobial activity of SnF2 formulated in a new stabilized matrix (currently marketed as Crest Gum Care), and demonstrate the utility of the PGRM method in elucidating specific mechanisms of action for antimicrobial agents.

Acetates↗
PubMed1995

Field trials with methoprene, temephos, and Bacillus thuringiensis serovar israelensis for the control of larval Culiseta melanura.

In 1992, Altosid (methoprene) pellets, Abate (temephos) 5 CG, and Bactimos (Bacillus thuringiensis serovar israelensis) granules were applied aerially to small field plots within a Culiseta breeding swamp. Aspects measured included the deposition and diffusion of larvicides into larval crypts and effects on larval Culiseta melanura and nontarget aquatic organisms. Formulations were deposited at approximately 50% of application rates. The presence of methoprene in 8 crypt water samples indicated that this larvicide was able to diffuse into Cs. melanura larval crypts. Methoprene was selected for evaluation in a large-scale field trial. In the spring of 1993, methoprene pellets applied to 25% of the study area were an effective larvicide against Cs. melanura. The inhibitory effect on pupae exceeded 81% over a 5-wk posttreatment period.

Animals↗
PubMed1994

A comparison of the performance of pig hearts perfused with pig or human blood using an ex-vivo working heart model.

The pathophysiology of xenograft hyperacute rejection is still poorly understood although it is believed to involve complement fixation to vascular endothelium, probably as a result of the presence of naturally occurring anti-species antibodies. Hyperacute rejection of pig hearts by human blood was studied in an ex-vivo working heart model. Cardiac performance and immunological reactions occurring in the perfusing blood were studied. Stroke work performed by pig hearts perfused with human blood and their survival (median 47 min: n = 10) was significantly reduced compared to survival (median 158 min: n = 10) and stroke work performed by pig hearts perfused with pig blood. Decomplementation of human blood resulted in improved performance and duration of the action (median survival > 240 min: n = 10) of hearts. Quantitative differences were seen in complement fixation between the groups. Our data demonstrate the central role of complement in the destruction of pig-to-man xenografts.

Animals↗
PubMed1994

Inhibition of tumor necrosis factor prevents myocardial dysfunction during burn shock.

Tumor necrosis factor-alpha (TNF) is a pluripotent cytokine that mediates many of the hemodynamic manifestations of endotoxic shock. To determine whether TNF is responsible for postburn myocardial dysfunction, we compared cardiac function (Langendorff preparation) in 49 guinea pigs 18 h after thermal injury. Group 1 (n = 15) was sham burned; all remaining animals received a 43% surface area burn under anesthesia. Group 2 (n = 15) received lactated Ringer solution (LR, 4 ml.kg-1.%burn-1). Group 3 (n = 9) received LR and drug vehicle. Group 4 (n = 10) received LR plus 1 mg of TNF inhibitor consisting of the human p80 TNF receptor linked to the Fc portion of human immunoglobulin G1, which was shown to specifically bind and neutralize TNF secreted by guinea pig peritoneal macrophages in vitro. Burn injury caused a significant fall in left ventricular pressure (LVP, from 86 +/- 2 to 62 +/- 3 mmHg, P < 0.05) and maximal rate of LVP rise (+) and fall (-) (+/- dP/dtmax) [from 1,365 +/- 42 to 1,109 +/- 44 mmHg/s (P < 0.05) and from 1,184 +/- 31 to 881 +/- 40 mmHg/s (P < 0.05), respectively], a decrease in time to peak systolic LVP (from 111 +/- 2 to 102 +/- 2 ms, P < 0.05), and a decrease in time to +dP/dtmax (from 57 +/- 1 to 48 +/- 1 ms, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Mode of action of fluoride: application of new techniques and test methods to the examination of the mechanism of action of topical fluoride.

Modern techniques in dental research continue to assist in the study of the mode of (anticaries) action of topical fluorides. The Plaque Glycolysis and Regrowth Model (PGRM) facilitates the standardized assessments of antimicrobial effects on plaque following use of test formulations in vivo without complications arising from coincident mineral reactivity. In vivo plaque glycolysis testing demonstrates that topically applied fluoride, at conventional levels found in dentifrices, has only modest effects on the metabolic (acid-producing) activity of dental plaque. Any 'plaque' contribution to fluoride efficacy must come from more subtle effects on plaque acidogenicity than those measured in PGRM. The 19-FMAS NMR (Magic Angle Spinning Nuclear Magnetic Resonance) technique provides unambiguous measures of the reaction products of F-enamel interactions. Studies have revealed a new 'reaction product' of fluoride-enamel interactions--designated as Non-Specifically-Adsorbed Fluoride, NSAF. This species, along with FAP (fluoroapatite), FHAP (fluorohydroxyapatite), and CaF2 (calcium fluoride), contributes to the remineralization/demineralization benefits of fluoride. pH cycling and in situ denture chip studies permit quantitative assessments to be made of the relative benefits of fluoride in promoting remineralization and in inhibiting demineralization. Results from pH cycling/in situ experiments are strongly supportive of Koulourides' 'Acquired Acid Resistance' concept, describing fluoride's decay-preventive effects. The continued application of new analytical/physical techniques and testing regimens to the study of fluoride anticaries mechanisms may lead to the development of improved fluoride agents/treatment modalities for the prevention of dental caries.

Analysis of Variance↗