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R C Williams

Publications and source records attributed to R C Williams.

At least 37 records · Page 2Linked to original sources
PubMed2000

Illness outbreak associated with Escherichia coli O157:H7 in Genoa salami. E. coli O157:H7 Working Group.

BACKGROUND: An outbreak of Escherichia coli O157:H7 infection was identified in the spring of 1998, with a 7-fold increase in the number of laboratory-confirmed E. coli O157:H7 cases in southern Ontario. This prompted an intensive investigation by local, provincial and federal public health officials. METHODS: Case interviews of 25 people from southern Ontario were conducted using a broad food history and environmental exposure survey. Laboratory investigations involved both case and food sampling. Specimens of foods sold locally and reportedly consumed by those affected were tested. Common suppliers of suspected foods were identified by cross-referencing suppliers' lists with stores frequented by those who fell ill. A case-control study involving 25 cases and 49 age-matched controls was conducted. This was followed by a comprehensive environmental investigation of the meat processing plant identified as the source of the E. coli. RESULTS: Thirty-nine outbreak-related cases occurred between April 3 and June 2, 1998. Of the 36 case specimens tested all were positive for E. coli O157:H7. The case-control study identified Genoa salami as the most probable (odds ratio 8 [confidence interval 2-35]) source of the outbreak. Samples of Genoa salami produced by the most commonly identified supplier later tested positive for E. coli O157:H7, and the pathogen matched the same pulsed-field gel electrophoresis pattern and phage type of the case specimens. INTERPRETATION: Our investigation, which led to a national recall of the brand of dry fermented Genoa salami identified as the source of the outbreak, supports an adherence to stringent manufacturing requirements for fermented meat products. A review of the Canadian standards for fermented meat processing and the effectiveness of their implementation is warranted.

Adolescent↗
PubMed2000

Analysis of potassium counter ion and inorganic cation impurities in pharmaceutical drug substance by capillary electrophoresis with conductivity detection.

Capillary electrophoresis with conductivity detection is a selective and quantitative method for the analysis of counter cations, such as potassium, in pharmaceutical drug substances. It is also a sensitive and specific technique for screening and measuring inorganic impurities in drug substance samples. Both counter ion and inorganic impurities can be measured in the same test.

Amidines↗
PubMed2000

Modulation of host inflammatory mediators as a treatment strategy for periodontal diseases.

Studies ranging from preclinical animal models to human clinical trials support the basic hypothesis that the inhibition of local arachidonic acid metabolites with nonsteroidal anti-inflammatory drugs slows periodontal disease progression. Data on modulation of other host mediators such as cytokines and NO remain restricted to laboratory or preclinical investigations, but appear promising. It is unlikely that such agents, following regulatory approval, will be used ubiquitously in patient populations, but rather may be targeted for at-risk patients. In the emerging field of periodontal medicine, patient cohorts are currently being identified with genetically based inflammatory mediator hyper-responses (48, 49, 68, 115). Such cohorts who respond to the endotoxin challenge posed by periodontitis with a robust release of cytokines or prostaglandins may benefit most in terms of slowing periodontitis progression and potentially improving systemic susceptibility (3, 67).

Animals↗
PubMed2000

Individual estimates of European genetic admixture associated with lower body-mass index, plasma glucose, and prevalence of type 2 diabetes in Pima Indians.

Individual genetic admixture estimates (IA) from European Americans (EAs) were computed in 7,996 members of the Gila River Indian Community (Arizona). Parental populations for the analysis were European Americans and full-heritage Pima Indians. A logistic regression was performed on 7,796 persons, to assess association of IA with type 2 diabetes. The odds ratio, comparing diabetes risk in full-heritage EAs with full-heritage Pima Indians, was 0.329 (95% confidence interval [CI] 0.225-0.482). Proportional-hazards analysis was performed on 5,482 persons who were nondiabetic at their first examination and 1,215 subjects who developed diabetes during the study. The hazard risk ratio for IA was 0.455 (95% CI 0.301-0.688). Nondiabetic persons had significantly more European IA. In nondiabetic Pimans, multivariate linear regressions of quantitative predictors of type 2 diabetes mellitus, including fasting plasma glucose, 2-h post-load plasma glucose, and body-mass index, showed significant inverse relations with IA when controlled for sex and age. These results illustrate the ongoing evolution of populations by the mechanism of gene flow and its effect on disease risk in the groups with admixture. When the two parental populations differ in disease prevalence, higher or lower risk is associated with admixture, depending on the origin of the admixed alleles and the relative magnitude of the disease prevalence in the parental populations. These data also illustrate the strong genetic components in type 2 diabetes and are consistent with one susceptibility locus common to obesity and diabetes.

Age Factors↗
PubMed2000

Assessment and management of periodontal infections: a medical-surgical approach.

Over the last 30 years, significant advances have been achieved in elucidating the etiology, pathogenesis, and treatment of periodontal diseases. A new paradigm has emerged that includes the initiation of disease by specific bacteria within a biofilm that stimulate an immunoinflammatory host response, resulting in host tissue destruction. Disease modifiers, which may be of genetic, environmental, or acquired origin, have been recognized as major determinants of disease severity and progression. Current treatment protocols include an assessment of risk factors to identify an individual's degree of susceptibility and therapeutic responsiveness. Basic and clinical research has resulted in the development of several strategies to identify specific bacteria and host-derived markers associated with disease progression. Preventive and therapeutic antimicrobial therapies, which use various delivery systems, have been devised to target drug placement to the infection site. More recently, host modulatory therapies have been created that inhibit disease progression through the reduction of inflammatory mediators. Finally, biological mediators, including growth and differentiation factors, have been used to enhance an individual's healing potential to achieve periodontal and bone regeneration. A combined medical-surgical approach is indicated for these new methods of diagnosis, prevention, and treatment of periodontal diseases, which will allow for earlier treatment interventions and improved patient outcomes.

Anti-Infective Agents, Local↗
PubMed2000

Understanding the pathogenesis of periodontitis: a century of discovery.

The twentieth century was an especially notable time for research advances into the understanding of the aetiology and the pathogenesis of periodontitis. Beginning in 1900, using dark-field preparations, investigators began to implicate certain microorganisms, such as amoebae, as causing periodontitis. Today, using modern molecular techniques, we believe we have identified the primary causative agents of adult periodontitis. In 1900, histological sections of periodontal tissues at autopsy provided clues as to how periodontal pockets probably formed. Today there is a wealth of cellular and molecular data that suggest the actual pathways that the susceptible host uses to initiate periodontal tissue destruction. We now also appreciate that periodontitis may be a significant risk factor for systemic disease. A very exceptional 'century of discovery' into the nature of periodontal diseases should now lead to a new era of better diagnosis, prevention and treatment for this ubiquitous disease.

Disease Susceptibility↗
PubMed1999

The concept of "risk" and the emerging discipline of periodontal medicine.

Dental clinicians intuitively weigh patient risks for developing disease and use that information for making treatment decisions and recommendations. Periodontitis, for instance, is one oral disease with documented risk factors including smoking, specific plaque bacteria and diabetes mellitus. While this link between systemic disease and periodontitis was thought to be unidirectional, mounting evidence in the last decade suggests that the relationship may be bi-directional. Cross sectional and case control studies indicate that periodontitis may confer two and seven-fold elevations in risk for cardiovascular disease and premature low birth weight respectively. While these early studies indicate potential associations between oral and systemic health, they support the central hypothesis that periodontitis triggers both local and systemic host inflammatory responses. Consequently, a new discipline, periodontal medicine, has emerged in dentistry which seeks to further define these interrelationships through scientific inquiry. Ultimately, this new knowledge may prove useful in intervention strategies to reduce patient risks and prevent systemic disease outcomes. This manuscript clarifies the concept of risk, traces the emergence of periodontal medicine and serves as a resource for the oral health professional in assessing and utilizing the current evidence on periodontal-systemic disease connections.

Bacteria, Anaerobic↗
PubMed1999

Retinoic acid promotes rod photoreceptor differentiation in rat retina in vivo.

Previous studies have indicated that retinoic acid (RA) promotes rod photoreceptor differentiation in dissociated cultures of rat retina and in zebrafish embryos. To determine whether RA will have the same affect in the mammalian retina in vivo, pregnant rats were given single i.p. injections of RA on the 18th and 20th days of gestation, and the retinas of the pups were analyzed for rods. HPLC showed that i.p. injections of RA substantially increased levels of retinal RA in the embryos. Embryonic exposure to RA caused an increase in the number of cells that differentiated as rod photoreceptors. There was a comparable decrease in the number of cells that differentiated as amacrine cells. These results demonstrate that RA promotes the differentiation of rods in vivo and further support the hypothesis that differentiation of rods is normally controlled partly by the RA concentration in the developing retina or RPE.

Animals↗
PubMed1999

Optimization and validation of chiral high-performance liquid chromatographic method for analysis of a fibrinogen (gpIIb/IIIa) receptor antagonist.

A chiral HPLC separation on an alpha 1-acid glycoprotein (AGP) column was developed for the separation of roxifiban, a fibrinogen receptor antagonist, from its related chiral impurities. The proposed method was optimized for mobile phase buffer concentration, organic modifier, and temperature using experimental design. The method was then validated for use in release testing of the roxifiban drug substance.

Amidines↗
PubMed1999

Chemical stability of an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist in solid dosage forms.

DMP 754 is an ester prodrug of a glycoprotein IIb/IIIa receptor antagonist that undergoes ester and amidine hydrolysis in the presence of excipients. A means for the stabilization of DMP 754 was needed for the formulation of a stable drug product. Incorporation of a pH modifier in the formulation was used to control the microenvironment pH to coincide with that of maximum stability for DMP 754. Stability of tablets and capsules manufactured by (a) trituration process, (b) dry granulation process, and (c) wet granulation process was evaluated in HDPE bottles. Formulations manufactured by the dry and wet granulation processes contained disodium citrate as the pH modifier. Although aqueous wet granulation of a hydrolyzable drug is usually avoided, tablets and capsules manufactured by wet granulation were more stable in this case than those manufactured by the dry granulation process. This was attributed to the more uniform distribution of the pH modifier. Although the compression process resulted in enhanced degradation of the binary blend of DMP 754 and anhydrous lactose, tablets manufactured by the wet granulation process were more stable than capsules manufactured by the same process. Decreasing excipient-to-drug ratio enhanced the stability of tablets manufactured by the wet granulation process.

Amino Acids↗
PubMed1999

Effect of different acids on solid-state stability of an ester prodrug of a IIb/IIIa glycoprotein receptor antagonist.

DMP 754 is an ester prodrug of a fibrinogen glycoprotein IIb/IIIa receptor antagonist. The purpose of this study was to determine whether the addition of acids to blends containing DMP 754 and anhydrous lactose could improve the stability at 40 degrees C/75% relative humidity. DMP 754 drug substance was stable at this accelerated condition. Blending of DMP 754 with anhydrous lactose accelerated the hydrolysis of both the ester and the amidine groups. The pH of a saturated solution of lactose is approximately 6, whereas the pH of maximum solution stability for the drug substance is approximately 4. Acids were incorporated into the blend so that the microenvironment would be more acidic and afford improved drug stability. Addition of acids decreased the rate of hydrolysis of the amidine group and this effect was more pronounced with stronger acids. However, the more acidic ingredients led to more rapid hydrolysis of the ester group.

Amino Acids↗
PubMed1999

Periodontitis-atherosclerosis syndrome: an expanded model of pathogenesis.

The early reports of a linkage between periodontitis and atherosclerosis have garnered further support by additional data generated by several investigative teams in many different countries. The evidence continues to suggest that periodontitis may be an important risk factor or risk indicator for cardiovascular pathology for some individuals. The term periodontitis-atherosclerosis syndrome (PAS) is proposed as a new diagnostic term to describe this condition in these individuals. Current evidence, albeit preliminary in nature, which describes a cluster of clinical signs and symptoms that are associated with this condition, is presented. It is clear that this syndrome will require considerable study and refinement before a definitive diagnosis and treatment plan can be formulated. Potential mechanisms by which systemic inflammation and infectious challenge of periodontal origin may serve as a potential modifier of cardiovascular disease are discussed in the context of a detailed working model of pathogenesis. This hypothetical model embraces many cellular and molecular components of atherogenesis and thromboembolic diseases from the perspective of periodontitis pathogenesis. Many aspects of the hypothetical model remain unproved; however, it is our opinion that only through the clarification of the mechanisms of pathogenesis can we ultimately construct a knowledge framework for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimize the deleterious effects of this chronic infectious and inflammatory condition on the cardiovascular system represents an unprecedented challenge to our profession.

Arteriosclerosis↗
PubMed1999

Growth and survival of uninjured and sublethally heat-injured Escherichia coli O157:H7 on beef extract medium as influenced by package atmosphere and storage temperature.

The effect of atmospheric composition and storage temperature on growth and survival of uninjured and sublethally heat-injured Escherichia coli O157:H7, inoculated onto brain heart infusion agar containing 0.3% beef extract (BEM), was determined. BEM plates were packaged in barrier bags in air, 100% CO2, 100% N2, 20% CO2: 80% N2, and vacuum and were stored at 4, 10, and 37 degrees C for up to 20 days. Package atmosphere and inoculum status (i.e., uninjured or heat-injured) influenced (P < 0.01) growth and survival of E. coli O157:H7 stored at all test temperatures. Growth of heat-injured E. coli O157:H7 was slower (P < 0.01) than uninjured E. coli O157:H7 stored at 37 degrees C. At 37 degrees C, uninjured E. coli O157:H7 reached stationary phase growth earlier than heat-injured populations. Uninjured E. coli O157:H7 grew during 10 days of storage at 10 degrees C, while heat-injured populations declined during 20 days of storage at 10 degrees C. Uninjured E. coli O157:H7 stored at 10 degrees C reached stationary phase growth within approximately 10 days in all packaging atmospheres except CO2. Populations of uninjured and heat-injured E. coli O157:H7 declined throughout storage for 20 days at 4 degrees C. Survival of uninjured populations stored at 4 degrees C, as well as heat-injured populations stored at 4 and 10 degrees C, was enhanced in CO2 atmosphere. Survival of heat-injured E. coli O157:H7 at 4 and 10 degrees C was not different (P > 0.05). Uninjured and heat-injured E. coli O157:H7 are able to survive at low temperatures in the modified atmospheres used in this study.

Carbon Dioxide↗
PubMed1999

A radiographic evaluation of bone healing around submerged and non-submerged dental implants in beagle dogs.

BACKGROUND: The rehabilitation of the oral cavity with dental implants has become a predictable treatment modality. However, there have been only a few direct comparisons evaluating the submerged and nonsubmerged placement techniques. The purpose of this study was to characterize radiographic peri-implant bone changes following the insertion of submerged and nonsubmerged implants in the beagle dog. METHODS: At the end of the extraction healing phase, 19 submerged and 19 nonsubmerged implants were randomly placed in a split-mouth study design and observed over an 18-week period. For submerged implants, a second stage surgery and transmucosal abutment attachment was performed at week 12. Standardized dental radiographs taken at baseline, week 12, and week 18 were used to measure peri-implant bone changes. The radiographs were analyzed with a simple computer assisted method. RESULTS: A total of 43 standardized radiographs were exposed to evaluate the 38 implants. During the study period, all submerged and nonsubmerged implants demonstrated peri-implant bone loss. At baseline, both submerged and nonsubmerged implants had similar bone levels (P > or = 0.05). When the mean peri-implant bone levels for submerged and nonsubmerged implants were compared from baseline to week 12, nonsubmerged implants had a significantly greater amount and rate of bone resorption than submerged implants (P < or = 0.05). Following week 12, the initially submerged implant had a significantly higher rate and amount of peri-implant bone loss than the nonsubmerged implants (P < or = 0.05). However, by the end of the study period, week 18, both submerged and nonsubmerged implants had comparable bone levels (P > or = 0.05). CONCLUSIONS: The study indicates that, although the temporal patterns of peri-implant bone resorption differed, there were no differences between submerged and nonsubmerged implants in the overall amount and rate of peri-implant bone loss.

Alveolar Process↗