Distribution of human papillomavirus types, cervical cancer screening history, and risk factors for infection in Manitoba.

OBJECTIVES: We conducted a study to investigate the prevalence of human papillomavirus (HPV) infections in an opportunistic sample of women in Manitoba, Canada. We inquired about risk factors associated with HPV infections and linked the HPV typing results with the cervical cancer screening history of the participants. METHODS: The study population included 592 women attending Papanicolaou (Pap) test clinics. After signing a consent form, participants were given a self-administered questionnaire on risk factors and received a conventional Pap test. Residual cells from the Pap tests were collected and sent for HPV typing. RESULTS: The mean age of the population was 43 years. A total of 115 participants (19.4%) had an HPV infection, 89 of whom had a normal Pap test. Of those who were HPV-positive, 61 (10.3%) had high-risk (Group 1) HPV. HPV-16 was the most prevalent type (15/115: 13.0% of infections). The most consistent risk factors for HPV infection were young age, Aboriginal ethnicity, higher lifetime number of sexual partners and higher number of sexual partners in the previous year. CONCLUSION: The prevalence of HPV types in Manitoba is consistent with the distributions reported in other jurisdictions. These data provide baseline information on type-specific HPV prevalence in an unvaccinated population and can be useful in evaluating the effectiveness of the HPV immunization program. An added benefit is in the validation of a proof of concept which links a population-based Pap registry to laboratory test results and a risk behaviour survey to assess early and late outcomes of HPV infection. This methodology could be applied to other jurisdictions across Canada where such capacities exist.

Phytophthora multivora sp. nov., a new species recovered from declining Eucalyptus, Banksia, Agonis and other plant species in Western Australia.

A new Phytophthora species, isolated from rhizosphere soil of declining or dead trees of Eucalyptus gomphocephala, E. marginata, Agonis flexuosa, and another 13 plant species, and from fine roots of E. marginata and collar lesions of Banksia attenuata in Western Australia, is described as Phytophthora multivora sp. nov. It is homothallic and produces semipapillate sporangia, smooth-walled oogonia containing thick-walled oospores, and paragynous antheridia. Although morphologically similar to P. citricola, phylogenetic analyses of the ITS and cox1 gene regions demonstrate that P. multivora is unique. Phytophthora multivora is pathogenic to bark and cambium of E. gomphocephala and E. marginata and is believed to be involved in the decline syndrome of both eucalypt species within the tuart woodland in south-west Western Australia.

Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742.

OBJECTIVE: To define the anti-inflammatory effects of PPARbeta/delta activation by use of the selective PPARbeta/delta ligand (GW0742) in a model of lipopolysaccharide (LPS)-induced pulmonary inflammation. METHODS: Male BALB/c mice were pretreated for three days with the PPARbeta/delta agonist, GW0742, prior to induction of LPS-mediated pulmonary inflammation. Bronchial alveolar lavage fluid (BALF) was analyzed for inflammatory cell influx and for levels of pro-inflammatory mediators. BALF-derived inflammatory cells were also collected for mRNA analysis. RESULTS: Pretreatment with GW0742 resulted in a significant decrease in leukocyte recruitment into the pulmonary space. Protein and mRNA levels of the pro-inflammatory cytokines IL-6, IL-1beta and TNFalpha in BALF were found to be significantly decreased in GW0742-treated animals (30 mg/kg). A significant decrease in granulocyte macrophage-colony stimulating factor (GM-CSF), a major regulator of neutrophil chemotaxis (via its downstream actions on TNFalpha and other cytokines/chemokines), activation and survival, was also noted in the BALF levels of GW0742-treated animals. CONCLUSIONS: The present study demonstrates that activation of PPARbeta/delta attenuates the degree of inflammation in a model of LPS-induced pulmonary inflammation and may therefore represent a novel therapeutic approach for the treatment of inflammation-mediated pathologies.

Development of a D-FISH method to detect DEK/CAN fusion resulting from t(6;9)(p23;q34) in patients with acute myelogenous leukemia.

The t(6;9)(p23;q34)-DEK/CAN fusion occurs with an incidence of 1-5% in adult patients with acute myelogenous leukemia (AML) and tends to have an unfavorable prognosis at diagnosis. Due to the subtle appearance of this chromosome rearrangement, both initial detection and minimal residual disease (MRD) tracking by conventional karyotyping can be difficult. Unfortunately, no commercial or previously published fluorescence in situ hybridization (FISH) strategies exist for this recurrent anomaly. We have developed a highly sensitive assay using dual-color, double-fusion FISH (D-FISH), which can be used both for initial detection and MRD monitoring. We analyzed archived bone marrow samples from 15 patients with a previously identified t(6;9)(p23;q34) and 10 corresponding post-treatment samples. The results demonstrate that our D-FISH method effectively identified all abnormal samples, including a low-level MRD sample that was considered to be normal by conventional cytogenetic analysis. Normal value ranges were established from 30 negative controls to be < 0.6% when 500 interphase nuclei were analyzed. The development of this sensitive D-FISH strategy for the detection of the t(6;9)(p23;q34) adds to the AML FISH testing repertoire, and is effective in the detection of low-level disease in post-treatment samples in these patients.

A modification to the experimental gingivitis protocol to compare the antiplaque properties of two toothpastes.

BACKGROUND AND AIMS: Randomised, blind, controlled experimental gingivitis and home-use study protocols are used to evaluate the efficacy of oral hygiene products. The present methodological study combined the two clinical trial designs to compare the preventive and therapeutic potentials of two toothpastes. MATERIAL AND METHODS: The study was a parallel group, randomised, double-blind design, initially involving 73 healthy dentate subjects. A 21-day experimental gingivitis protocol was combined with a 6-week (42 days) home-use protocol. At baseline, modified gingival index (MGI), gingival index (GI) and gingival bleeding (GB) were recorded. A dental prophylaxis was then performed. Subjects were allocated to either control fluoride or stannous fluoride toothpaste based on gender and GI. During the first 21-day period, subjects applied the allocated toothpaste, for 1 min twice a day, to a group of teeth in a plastic shield and brushed the remaining teeth with the same paste. From day 21 the shield was not placed, and subjects brushed all teeth with the toothpaste for 1 min twice per day up to day 42. MGI, GB and a plaque index (PI) were recorded on days 21 and 42. RESULTS: Sixty-nine and 67 subjects completed to days 21 and 42, respectively. For shielded teeth, PI, MGI and GB increased to day 21 and then after ceasing the use of the shield decreased to day 42. At day 21, PI favoured the stannous fluoride toothpaste, but differences did not achieve statistical significance for any parameter at days 21 or 42. For unshielded teeth, there were no significant differences between the toothpastes for any parameter at either time point. CONCLUSION: : The feasibility of combining two gingivitis clinical trial methodologies appears proven, and data on both the preventive and therapeutic chemical and mechanical efficacy of toothpastes can be obtained through such protocols. Specifically from the present study and consistent with some other reports, the plaque inhibitory properties of the stannous fluoride product are limited and do not always translate into an antiplaque/antigingivitis effect.

Three Clonal Lineages of Phytophthora cinnamomi in Australia Revealed by Microsatellites.

ABSTRACT The genetic structure of populations of Phytophthora cinnamomi, a pathogen of an enormous variety of woody plants, was investigated using microsatellites. Three intensively sampled disease sites in southwest Australia were analyzed along with a large culture collection of Austra-lian isolates and some isolates from elsewhere in the world. The mutation in the four microsatellite loci analyzed revealed spatial patterns at the disease sites that correlated with the age of the infestation. Only three clonal lineages were identified in Australian populations and these same clonal lineages were present in worldwide populations, where it is suggested that a limited number of clonal lineages have spread in most regions. No evidence for sexual reproduction between these clonal lineages in Australia has been found even though the pathogen has the opportunity. Instead, mitotic recombination is frequent within the clonal lineages. The implications of this are discussed.

A method to compare four mouthrinses: time to gingivitis level as the primary outcome variable.

BACKGROUND AND AIM: The experimental gingivitis model is a well-established method in comparing the chemical antiplaque activity of agents and products. The aim of the present study was to use time in order to achieve an exit level of bleeding on probing (BOP) as the primary outcome variable. METHODS: The study was a single blind, randomised four treatment parallel group design employing 76 healthy volunteers. The cohort was accepted into the study proper if they achieved a level of /= 50% BOP. Using the baseline and exit BOP, MGI and plaque, a deterioration rate for each parameter was derived and used as the unit of analysis. RESULTS: There were highly significant treatment differences for all three parameters. Paired analyses revealed chlorhexidine was highly significantly more effective than the other rinses for all three parameters. CPC and triclosan were not different from the control for BOP, but CPC was significantly different from the control for MGI and plaque, and triclosan was different from the control for plaque. There were no differences between the CPC and triclosan rinses. CONCLUSIONS: The method achieved the expected result of differentiating between the chlorhexidine and the other rinses. Some modification of the method, primarily to group sizes, should improve specificity. The method has the considerable volunteer appeal of early exit, particularly when allocated to control or low activity treatments for plaque.

Inhibition of inducible nitric oxide synthase by acetamidine derivatives of hetero-substituted lysine and homolysine.

The synthesis and in vitro evaluation of the acetamidine derivatives of hetero-substituted lysine and homolysine analogues have identified potent inhibitors of human nitric oxide synthase enzymes, including examples with marked selectivity for the inducible isoform.

Risk and prevention of hepatitis C virus infection. Implications for dentistry.

BACKGROUND: The occupational risk of hepatitis C virus, or HCV, infection in dentistry is very low. Nonetheless, the lack of an effective vaccine, the high rates of chronic infection and the limited effectiveness of treatment may cause concern for dental workers who come into contact with blood in their daily practices. DESCRIPTION OF THE DISORDER: The authors discuss the natural history, diagnosis and treatment, and patterns of transmission of HCV infection, including the Centers for Disease Control and Prevention's recommendations for management and follow-up of health care workers after occupational exposure to HCV. CLINICAL IMPLICATIONS: In the absence of an effective vaccine or postexposure prophylaxis, prevention of occupational transmission of HCV in dental settings continues to rely on the use of universal precautions, including barrier precautions and the safe handling of sharp instruments.

N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity.

Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3-(aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2-furanylamidine (77) (Ki-nNOS = 0.006 microM; Ki-eNOS = 0.35 microM; Ki-iNOS = 0.16 microM). Finally, alpha-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (Ki-nNOS = 0. 011 microM; Ki-eNOS = 1.1 microM; Ki-iNOS = 0.48 microM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.

Substituted N-phenylisothioureas: potent inhibitors of human nitric oxide synthase with neuronal isoform selectivity.

S-Ethyl N-phenylisothiourea (4) has been found to be a potent inhibitor of both the human constitutive and inducible isoforms of nitric oxide synthase. A series of substituted N-phenylisothiourea analogues was synthesized to investigate the structure-activity relationship of this class of inhibitor. Each analogue was evaluated for human isoform selectivity. One analogue, S-ethyl N-[4-(trifluoromethyl)phenyl]isothiourea (39), exhibited 115-fold and 29-fold selectivity for the neuronal isoform versus the inducible and endothelial derived constitutive isoforms, respectively. Studies have shown the substituted N-phenylisothiourea 39 binds competitively with L-arginine.

Differential expression of type I cytokeratins in hamster cheek pouch epithelium following treatment with dimethylbenzanthracene.

Cytokeratin (CK) expression in untreated, paraffin-treated or dimethylbenzanthracene (DMBA)-treated hamster cheek pouch epithelium was investigated utilizing monoclonal antibodies AE1 or AE3, which react with type I or type II CKs, respectively, and by in situ hybridization utilizing type I CK-specific probes. The latter were isolated from a cDNA library of hamster cheek pouch mRNA and designated CK 13 and CK 10 based on their respective homologies (> 95% amino acids) with murine CK 13 and human CK 10. Treatment of hamster cheek pouch epithelium with DMBA resulted in increased expression of type I CK, detected immunohistochemically with monoclonal AE1, but decreased expression of type II CKs detected with AE3. Despite an overall increase in type I CKs, in situ hybridization demonstrated differential expression of type I CKs with altered distribution of CK 13 mRNA and reduced expression of CK 10 mRNA, providing additional sensitive markers for DMBA-associated changes in CKs. These changes were constant at 2 to 22 weeks in the pre-neoplastic and neoplastic epithelium following the initial application of DMBA.

The clinical practice developmental model: the transition process.

The authors report their hospital's experience in replicating Benner's novice-to-expert clinical nursing practice model, called the Clinical Practice Developmental Model. The authors describe the outcomes of an exploratory, qualitative study conducted to understand staff nurses' perceptions of their transition experience from a traditional clinical ladder for advancement and recognition to the theoretically based clinical practice developmental model. The findings of this study identify critical factors that influenced nurses' perceptions and describe positive and negative outcomes of transition. Specific recommendations to facilitate organizational changes for the nurse executive and the individual nurse are discussed.

Influence of marginal configuration and porcelain addition on the fit of In-Ceram crowns.

The fit of In-Ceram copings and crowns was investigated in a laboratory study. Two methods were used, one a direct sectioning technique and the other a cement analogue technique using addition-cured polyvinylsiloxane impression material. The former method involved 40 crowns cemented and sectioned on their respective electroformed silver dies. For the second method, 80 analogues were embedded and sectioned. All measurements were made using a Reflex microscope. This showed In-Ceram crowns and copings to fit well with marginal openings and ranging from 1 to 63 microns and a mean of 19 microns. No significant difference in fit was found between chamfer margins and shoulder margins. The addition of porcelain to the In-Ceram coping and repeated firing cycles involved in building a crown did not alter the fit. It is concluded that In-Ceram crowns fit well in comparison to other crown types.

Biofilm and the dental office.

The author provides a brief overview of the basic processes involved in biofilm formation and explores the implications these biofilms have for health care facilities such as hospitals and dental offices. Included with this article are suggestions dentists may consider for improving water quality and a white paper on waterlines adopted by the ADA.

Osseointegrated implants: a review of the literature.

The success of osseointegrated implants as a treatment option is extremely high. In recent years the emphasis in implant development has moved towards improved aesthetics. This paper reviews some of the recent advances associated with aesthetics and implant supported restorations. The techniques of bone grafting and guided tissue regeneration have allowed more ideal placement of implant fixtures in many situations. Implant companies continue to improve their components making implant supported prostheses possible for a wider variety of patients. Further advances in the management of the soft tissues, particularly the interdental papillae, are required to optimise aesthetic results.

A review of the current approaches to the management of the severely reduced dentition.

The severely reduced dentition is a continual challenge to the treatment planning skills of the restorative dentist. This paper examines the need for treatment in the context of oral function, social requirements and related disease processes. The philosophy for management should be based on sound knowledge of the outcomes of treatment options. This paper highlights the relevant factors to be assessed in treatment planning for the severely reduced dentition.

Changes in cytokeratins following treatment of hamster cheek pouch epithelia with hyperplastic or neoplastic agents.

The effects of four different hyperplastic agents and of the carcinogen DMBA on cytokeratin expression in hamster cheek pouch epithelia were compared. Reversible hyperplasia was produced by the application of either oil of turpentine, vitamin A or TPA. No hyperplastic changes were produced by application of EPP. Apart from the transient appearance of a 45 kDa cytokeratin in one group treated with vitamin A, the immunohistochemical staining patterns and immunoblot profiles of cytokeratins from cheek pouches treated with each of the hyperplastic agents were identical to controls. Following application of DMBA, the cytokeratins stained with increased intensity in the spinous and granular cell layers. This was associated with increased amounts of 42-56 kDa cytokeratins and decreased production of 62-75 kDa cytokeratins. Monoclonal antibody AE1 detected a 45 kDa cytokeratin in extracts of DMBA-treated epithelia that was not detected in untreated epithelial extracts. Monoclonal antibody AE3 detected an additional 54 kDa cytokeratin band in extracts of DMBA-treated epithelia. These cytokeratin changes were present in preneoplastic epithelia and maintained in neoplastic epithelia.

MDR-TB. Another challenge from the microbial world.

Beginning in 1985, the long decline in TB cases was dramatically reversed; from 1985 through 1992 reported cases increased 20.1 percent nationally. Two characteristics of this resurgent epidemic are unique: its prevalence among immunocompromised HIV-infected people and the emergence of multidrug-resistant TB. Current epidemiological trends, demographics and treatment approaches are discussed, as well as the implications MDR-TB holds for dentistry.