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Biomedical subjects

P D Riggs

Publications and source records attributed to P D Riggs.

At least 19 recordsLinked to original sources

Development of butyl elastomer/methacrylate monomer systems as denture soft lining materials.

Previous studies have shown elastomer/methacrylate monomer formulations to have good strength; however, water uptake was high and they also suffered from oxidation. This study has looked at the use of three different butyl elastomers, well known for their oxidation resistance, butyl (PB), chlorobutyl (PCB) and bromobutyl (PBB). The tensile and water uptake properties of the three elastomers gelled with ethyl hexyl methacrylate containing 1% ethylene glycol dimethacrylate and 1% lauryl peroxide (5+ formulation from previous studies) were studied. Water uptake of the pure elastomers was also measured. Tensile strengths were low (PCB5+ = 3.09+/-0.12 MPa and PBB5+ = 3.90+/-0.36 MPa); however, elongation to break values were high (PCB5+ = 797+/-17% and PBB5+ = 599+/-13%). Water uptake was high and protracted with none of the formulations reaching equilibrium. The PCB5+ had the highest uptake (approximately 6% at 203 days) with that for PBB5+ and PB5+ at a similar level (approxiamtely 4% at 203 days). None of the materials showed any sign of oxidation. The PBB proved to be the most suitable of the three elastomers for further development in soft lining formulations.

Denture Liners↗

Nuclear magnetic imaging of an osmotic water uptake and delivery process.

The water absorption of NH4F-doped silicone cylinders was studied by spin-echo Fourier nuclear magnetic resonance imaging, in conjunction with gravimetric (mass uptake) and ionic concentration (release of NH4F) measurements. The addition of NH4F greatly increases the water uptake as the inclusions are surrounded by droplets of water when wetted by water diffusing in the polymer. These droplets then expand due to the osmotic pressure difference between the internal droplet and external solution; this expansion is opposed by an elastic restraining force. The rate of ingress into the polymer will depend on the relative chemical potential of water associated with the polymer and the droplet, as well as the diffusion coefficient. Later stages of the absorption process are dominated by the droplets. The dilution of the droplets (from water diffusing into the droplets) slowly reduces the chemical potential driving the process. Hence, the later stages occur without any notable concentration gradient but a slight chemical potential gradient. If the droplet expansion exceeds that which can be restrained by the material, failure around the droplet occurs resulting in the release of the salt and the solution within the droplet.

Ammonium Compounds↗

Blends of isoprene-styrene/methacrylate monomer systems as denture soft lining material.

This work further develops the concept of using an elastomer gelled with methacrylate monomers to produce a methacrylate-based soft lining material without the use of a plasticizer. An isoprene-styrene (SIS) block copolymer was mixed with methyl methacrylate (MMA) and 1,6-hexandiol dimethacrylate (HDMA). The HDMA was used as a cross-linking agent. The elastomer/monomer ratios were maintained at 50/50 whereas the monomers ranged from 0 to 100%) HDMA. Mechanical properties and water absorption/desorption characteristics were used to assess the effect of varying the monomer compositions. The results indicated that phase separation took place, in particular at high HDMA content. This significantly increased the Young's modulus and decreased the elongation to break. Generally, the water uptake tended to decrease with increasing HDMA content, reflecting the effect of modulus. Second absorption cycles gave higher uptake values compared to the first. Formulations with a high amount of HDMA gave materials with modulus values too high for soft lining applications. This suggests that the optimum formulation requires a compromise between modulus and water uptake.

Absorption↗

Development of novel elastomer/methacrylate monomer soft lining materials.

An earlier study identified a formulation comprising a butadiene/styrene copolymer (PBS) gelled with ethyl hexyl methacrylate (5 + formulation) as a potential denture soft lining material. It had good mechanical properties but water uptake was high as a result of the presence of a separating agent. This study has compared the tensile and water absorption properties of four elastomers free from separating agent (three butadiene/styrene, HBS, EBS, SBS, and one isoprene/styrene, SIS) with those of PBS all using the 5 + formulation. HBS is emulsion polymerized; the others are solution polymerized. SIS5 + had the better tensile properties whereas HBS5 + had the lowest water uptake. All the other 5 + formulations had higher uptakes than PBS5 +, which is thought to be due to the presence of hydrophilic groups from the solution polymerization process. All materials showed some sign of oxidation. Emulsion polymerized elastomers are regarded as less suitable for medical uses than the solution polymerized alternatives. Of these, SIS5 + seems to be less prone to oxidation and has the better mechanical properties so was considered to be the most suitable material for further development.

Journal Article↗

Chlorhexidine release from room temperature polymerising methacrylate systems.

A series of different methacrylate monomers (with either 1 or 2.5% dimethyl-p-toluidine, DMPT) was gelled with poly(ethyl methacrylate) powder (containing benzoyl peroxide) thus forming a room temperature curing system. When doped with 5.625% chlorhexidine diacetate the release from the tetrahydrofurfuryl methacrylate-based samples was considerably greater than that from other methacrylate monomers. This seems to be due to the formation of channels in the polymer. Nuclear magnetic resonance spectroscopy, of solutions that the samples were immersed in, showed chlorhexidine was indeed being released from the polymer. It also showed that doping the polymer with chlorhexidine hindered the polymerisation, resulting in a higher level of residual monomer and low molecular weight components being leached from the polymer. The DMPT also affected the polymerisation with greater leaching from the 2.5% DMPT sample.

Anti-Infective Agents, Local↗

3He ion-beam analysis of water uptake and drug delivery.

3He ion-beam analysis utilises a micronuclear reaction analysis (of deuterium and carbon) and microparticle induced X-ray emission (in this case silicon and chlorine), to determine an elemental map of the surface of a sample. This study used D(2)O to model the behaviour of water in poly(tetrahydrofurfuryl methacrylate-polyethyl methacrylate) and chlorhexidine diacetate doped silicone elastomers. The poly(tetrahydrofurfuryl methacrylate-polyethyl methacrylate) systems demonstrated an initial Fickian absorption process (diffusion coefficient 1.1 x 10(-11) m(2)s(-1)) which indicated the 2-stage nature of the polymer's absorption kinetics. The doped silicone samples demonstrated an osmotic mechanism for the controlled release of drugs, with correlation between the D(2)O and the chlorhexidine diacetate inclusions increasing during the experiment. The technique proved valuable in the analysis of delivery polymers and will undoubtedly have further applications in the development of drug delivery systems.

Chlorhexidine↗

Relationship of ADHD, depression, and non-tobacco substance use disorders to nicotine dependence in substance-dependent delinquents.

This study used standardized interviews to examine the relationship of attention deficit hyperactivity disorder (ADHD), major depression (MDD), and other illicit substance use disorders (SUD) to onset and severity of nicotine dependence in 82 female and 285 male adolescents with conduct disorder (CD) and SUD. Results indicate that both ADHD and MDD significantly contribute to severity of nicotine dependence in delinquents with SUD. ADHD is further associated with earlier onset of regular smoking in males. Severity of non-tobacco SUD also was related directly to nicotine dependence severity in both males and females, and to earlier onset of smoking in males. Our findings illuminate the contribution of comorbidity to nicotine dependence and its relationship to other SUD severity among adolescents with CD and SUD and highlight the need for coordinated assessment and treatment of smoking cessation along with concurrent treatment of other drug use and psychiatric comorbidity such as ADHD and MDD in such youths.

Adolescent↗

The water uptake of poly(tetrahydrofurfuryl methacrylate).

Poly(tetrahydrofurfuryl methacrylate) possesses some unique characteristics with respect to its biocompatibility and behaviour in water. The water uptake is high (>70%) and very slow (over 3 yr), but the material remains rigid throughout the process. The mechanism behind the uptake is in two stages; an initial Fickian stage, then as the matrix approaches saturation (about 3 wt%) a second clustering mechanism takes over. The rate of uptake of the second stage of the uptake is controlled by creep (or stress relaxation), and the chemical potential driving the uptake from clustering of the furfuryl rings of the polymer. If clustering or the creep is prevented (by appropriate co-polymerisation) the polymer behaves in an ideal, Fickian manner.

Absorption↗

Asp34 of PvuII endonuclease is directly involved in DNA minor groove recognition and indirectly involved in catalysis.

The PvuII restriction endonuclease is a homodimer that recognizes and cleaves the DNA sequence 5'-CAGCTG-3' in double-stranded DNA, and the structure of this enzyme has been reported. In the wild-type enzyme, Asp34 interacts with the internal guanine of the recognition sequence on the minor groove side. The Asp34 codon was altered to specify Gly (D34G), and in vitro studies have revealed that the D34G protein has lost binding specificity for the central G.C base-pairs, and that it cuts the canonical sequence with 10(-4)-fold reduced activity as compared to the wild-type enzyme. We have now determined the structure at 1.59 A resolution of the D34G PvuII endonuclease complexed with a 12 bp duplex deoxyoligonucleotide containing the cognate sequence. The D34G alteration results in several structural changes relative to wild-type protein/DNA complexes. First, the sugar moiety of the internal guanine changes from a C2'-endo to C3'-endo pucker while that of the 3' guanine changes from C3'-endo to C2'-endo pucker. Second, the axial rise between the internal G.C base-pairs is reduced while that between the G.C and flanking base-pairs is expanded. Third, two distinct monomeric active sites are observed that we refer to as being "primed" and "unprimed" for phosphodiester bond cleavage. The primed and unprimed sites differ in the conformation of the Asp58 side-chain, and in the absence from unprimed sites of four networked water molecules. These water molecules, present in the primed site, have been implicated in the catalytic mechanism of this and other endonucleases; some of them can be replaced by the Mg2+ necessary for cleavage. Taken together, these structural changes imply that the Asp34 side-chains from the two subunits maintain a distinct conformation of its DNA substrate, properly situating the target backbone phosphates and indirectly manipulating the active sites. This provides some insight into how recognition of the specific DNA sequence is linked to catalysis by the highly specific restriction endonucleases, and reveals one way in which the structural conformation of the DNA is modulated coordinately with that of the PvuII protein.

Aspartic Acid↗

Evaluating the effect of soft lining materials on the growth of yeast.

STATEMENT OF PROBLEM: Soft lining materials continue to have a place in clinical removable prosthodontics. However, there is an increased probability of yeast colonization on soft lining materials. PURPOSE: This study (1) assessed a method of evaluating the effect of long-term soft lining materials on the growth of yeast and (2) investigated the effect five soft lining materials had on the growth of three species of yeast. MATERIAL AND METHODS: Coe Supersoft, Novus, and three experimental soft lining materials were investigated together with Candida albicans, Candida tropicalis, and Issatchenkia orientalis (formerly Candida krusei) yeasts. Strips of soft lining material incubated on blood agar plates were examined for inhibition of the growth of yeast. Soft lining materials soaked in sterile trypticase soya broth or water were inoculated with yeast and incubated. The change in colony forming units per milliliter from the initial load of yeast at 3 days was measured. Statistical analysis was performed with an independent paired Student t test. RESULTS: Inhibition of yeast growth occurred for two soft lining materials. Despite the presence of sufficient viable organisms, differences between the initial load of yeast and the 3-day results were mostly small, both for the test and control groups, suggesting that the material does not support the growth of the tested yeast during this period. CONCLUSIONS: The often described increased prevalence of yeast associated with soft lining materials in the oral environment is likely related to readily available nutrients in the mouth and the difficulty in maintaining and cleaning these materials.

Acrylic Resins↗

An open trial of bupropion for ADHD in adolescents with substance use disorders and conduct disorder.

OBJECTIVE: Adolescents with conduct disorder (CD) and substance use disorders (SUD) have higher rates of comorbid attention-deficit/hyperactivity disorder (ADHD) than those without CD and SUD. Comorbid ADHD may contribute to more severe SUD. Treatment of ADHD may enhance effective treatment of substance abuse and behavior problems, yet there are few data regarding pharmacological treatment of ADHD in such youths. METHOD: Pilot data are presented from a 5-week, open-label bupropian trial in 13 nondepressed adolescent boys in a residential treatment program focusing on substance and behavioral treatments. All had diagnoses of ADHD, CD, and SUD. Patients' doses were titrated to a maximum fixed daily dose of 300 mg of bupropion. The Conners Hyperactivity Index and Daydream Attention scores, along with Clinical Global Impressions Severity of Illness (CGI-S) ratings, were obtained at baseline and at the fifth week of treatment. RESULTS: Subjects' mean Conners Hyperactivity Index score declined from 75.5 to 65.4 (p < .01, Wilcoxon signed rank test) (13% decline). The mean Daydream Attention score declined from 59.5 to 53.6 (p < .02, Wilcoxon signed rank test) (10% decline). Mean CGI-S declined from 4.9 to 3.0 (p < .002, Wilcoxon signed rank test) (39% decline). CONCLUSIONS: These preliminary data suggest that bupropion may be a useful treatment for ADHD in adolescents with CD and SUD; they suggest the need for a controlled trial of bupropion in such youths.

Adolescent↗

Catalytic and DNA binding properties of PvuII restriction endonuclease mutants.

The role of particular residues of the PvuII endonuclease in DNA binding and cleavage was studied by mutational analysis using a number of in vivo and in vitro approaches. While confirming the importance of residues predicted to be involved directly in function by the crystal structure, the analysis led to several striking results. Aspartate 34, which contacts the central base pair of the PvuII site (5'-CAGCTG-3') through the minor groove, plays a critical role in binding specificity. A D34G mutant binds with high affinity to any of the sequences in the set CANNTG, although its low level of cleavage activity acts only on the wild-type site. In addition, a His to Ala mutation at the residue that contacts the central G and is predicted to be blocked by PvuII methylation still requires the PvuII methylase to be maintained in vivo, arguing against this hypothesis as the only mechanism for methylation protection. Finally, four of the five mutations that reduce cleavage activity while still exhibiting binding in the gel shift assay are at residues that form DNA- or subunit-subunit contacts rather than in the catalytic center. This provides further evidence for a strong linkage between specific binding and catalysis.

Catalysis↗

Influences on adolescent substance dependence: conduct disorder, depression, attention deficit hyperactivity disorder, and gender.

OBJECTIVE: In adolescents, conduct disorder (CD), attention deficit hyperactivity disorder (ADHD), and depression are frequently comorbid with substance dependence (SD). We hypothesized that the prevalence and severity of CD, major depressive disorder (MDD), and ADHD would differ by gender, and that these conditions would associate differentially with severity of SD in males and females. METHODS: We examined these issues, using standardized diagnostic interviews, in 285 male and 82 female adolescents referred for comorbid CD and SD. RESULTS: Males and females did not differ significantly in severity of substance involvement, MDD, or ADHD, but males had more severe CD. MDD severity was the only variable significantly associated with SD severity for females, while for males, severity of CD combined with MDD and ADHD was significantly associated with SD severity. CONCLUSIONS: Among referred adolescents, CD, MDD, and ADHD may all be important concomitants of SD in males, while in females, depression may be the primary variable related to SD.

Adolescent↗

Influence of additives on the water uptake of hydrosilanized silicone rubbers.

Water uptake characteristics of a silicone polymer containing additives of varying solubility have been investigated. A hydrophobic silica, a sparingly soluble agent and a soluble catalyst were added to a stoichiometrically balanced hydrosilanized silicone polymer (the inherent absorption of which was 0.09 wt%). The diffusion coefficients for desorption of all materials were of the order 10(-6) cm2s-1, whereas the diffusion coefficients for absorption showed a decrease with increasing hydrophilicity and solubility of the additive. The greater the solubility of the additive, the more prolonged the uptake and the greater the deviation from classic diffusion theory.

Absorption↗

Fluoxetine in drug-dependent delinquents with major depression: an open trial.

Although fluoxetine might be more effective than placebo for treating adolescent depression without major comorbidity, little is known about the response of depressive symptoms to antidepressants in adolescents with comorbid conduct disorder (CD) and substance use disorders (SUD). Male adolescents, who remained or became depressed after > or = 1 month of abstinence from abused substances during residential treatment for SUD, were treated in an open trial for > or = 7 weeks with a fixed dose of 20 mg of fluoxetine. The eight adolescents (ages 14-18 years) with CD, SUD, and major depression were not in drug withdrawal or receiving other pharmacotherapy. A > or = 50% improvement was observed in mean scores on Ten Point Depression Scale rated by clinician (p < 0.01) and patients (p < 0.01), Carroll Self-Ratings for depression (p < 0.02), and Severity of Illness scores on the Clinical Global Impression (p < 0.01). Of the eight adolescents, seven showed marked improvement and wished to continue fluoxetine after the trial. Side effects were mild and transient. No subject required dosage reduction or discontinuation of medication because of side effects. Fluoxetine appeared useful in treating substance-dependent delinquents whose major depressions persisted or emerged after 4 weeks of abstinence. These preliminary findings justify a controlled trial in such youths.

Adolescent↗

Contribution of ADHD symptoms to substance problems and delinquency in conduct-disordered adolescents.

We examined adolescents with conduct disorder (CD) and substance problems to determine if those with attention deficit hyperactivity disorder (ADHD) symptomatology had more severe delinquency and substance involvement. ADHD symptomatology was assessed in two ways: (1) by self-reports using the Diagnostic Interview Schedule for Children (DISC) and (2) by use of DISC plus reports of others (parents, program staff, and program teacher). We divided boys into three ADHD groups based on DISC: those who met criteria, those who reported at least eight current symptoms, and those who reported fewer than eight symptoms. We also divided the same boys into two groups: those with reports of ADHD by two or more sources and those without this multisource ADHD. Examining these definitions of ADHD revealed that boys with either self- or multisource ADHD had more CD symptoms, earlier age of CD onset, more substance dependence diagnoses, and more comorbid depression and anxiety.

Adolescent↗

An open trial of pemoline in drug-dependent delinquents with attention-deficit hyperactivity disorder.

OBJECTIVE: Adolescents with conduct disorder and substance use disorders have high rates of comorbid attention-deficit hyperactivity disorder (ADHD); ADHD may contribute to the severity and persistence of substance use disorders and antisocial behaviors. Treatment of ADHD may help patients utilize substance and other behaviorally focused treatment. Yet little is known about the response of ADHD symptoms to psychopharmacological intervention in substance-dependent delinquents. METHOD: Pilot data are presented for 13 male adolescents with conduct disorder, substance use disorders, and ADHD, in a residential substance use treatment program. Patients were treated with pemoline. Scores from the Conners Hyperactivity Index and continuous performance tasks were obtained at baseline and after about 1 month of treatment with pemoline. Physical activity measurements were also assessed at baseline and 1 month. Postmedication assessments were obtained after at least 1 week at maximal dosage (1.2 to 3.3 mg/kg). RESULTS: Mean Conners Hyperactivity Index scores declined 13.9% (p < or = .002) and mean motility declined 7% (p < or = .04) with pemoline treatment. Continuous performance task scores did not change. CONCLUSIONS: Preliminary data indicate that pemoline may be a useful treatment for ADHD in substance-dependent delinquents; the authors propose a controlled trial of pemoline in such youths.

Adolescent↗