The road to ruin: the formation of disease‐associated oral biofilms

Oral Diseases (2010) 16 , 729–739 The colonization of oral surfaces by micro‐organisms occurs in a characteristic sequence of stages, each of which is potentially amenable to external intervention. The process begins with the adhesion of bacteria to host receptors on epithelial cells or in the salivary pellicle covering tooth surfaces. Interbacterial cell–cell binding interactions facilitate the attachment of new species and increase the diversity of the adherent microbial population. Microbial growth in oral biofilms is influenced by the exchange of chemical signals, metabolites and toxic products between neighbouring cells. Bacterial cells on tooth surfaces (dental plaque) produce extracellular polymers such as complex carbohydrates and nucleic acids. These large molecules form a protective matrix that contributes to the development of dental caries and, possibly, to periodontitis. The identification of key microbial factors underlying each step in the formation of oral biofilms will provide new opportunities for preventative or therapeutic measures aimed at controlling oral infectious diseases.     

Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report.

The Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of "ancillary therapy and supportive care" embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach.     

Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis

Almaguer‐Mederosa LE, Falcón NS, Almira YR, Zaldivar YG, Almarales DC, Góngora EM, Herrera MP, Batallán KE, Armiñán RR, Manresa MV, Cruz GS, Laffita‐Mesa J, Cyuz TM, Chang V, Auburger G, Gispert S, Pérez LV. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis. Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32–79 units. Using a Kaplan–Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34–45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive‐testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2.     

Designing an oral mucositis assessment instrument for use in children: generating items using a nominal group technique

Goals of work  There was a need to develop a mucositis instrument that would be specific for use with children. This paper describes the step of generating items in the process of developing a new instrument for the assessment of oral mucositis in children. Materials and methods  Nine health care professionals with expertise in pediatric cancer, mucositis assessment, and oral assessment in children were invited to participate in a nominal group technique to generate items that should be included in an instrument. Results  Thirty items were generated initially. Voting processes established that six of these items were thought to be necessary for inclusion: (1) presence of ulcers, (2) pain assessment, (3) amount of pain medication received, (4) effect on eating, (5) drooling–pooling of saliva, and (6) effect on drinking. Using these six items, an initial draft of an instrument was developed that could be used to assess oral mucositis in children, namely, the Children’s International Mucositis Evaluation Scale. Conclusion  The six items generated by this process provided the basis for a simple, feasible, and reliable instrument. With increased clinical research investigating interventions to reduce and prevent oral mucositis, such an instrument will be critical to the effective conduct of this research in children. Further testing of this instrument is necessary.     

Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients

BACKGROUND:

Mammalian target of rapamycin (mTOR) inhibitors may have efficacy as an intervention for advanced malignancies. Oral ulceration (OU), reported as mucositis, has been a dose‐limiting toxicity for this new class of agents. An analysis of the appearance, course, and toxicity associations of mTOR inhibitor‐associated stomatitis (mIAS) demonstrated that the condition is distinct from conventional mucositis (CM) and more closely resembles aphthous stomatitis.

METHODS:

Safety data from 78 solid tumor patients enrolled in 2 Phase 1, multicenter trials of the mTOR inhibitor deforolimus (AP23573, MK‐8669) were evaluated. Adverse events (AEs) based on National Cancer Institute Common Toxicity Criteria for National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0) criteria were coded, consolidated, and stratified according to the presence or absence and duration of concordant OU. The relation between OU and other AEs was analyzed.

RESULTS:

Treatment‐emergent AEs were reported in 91% of 78 study participants. OUs were reported in 66%, appeared within 5 days of deforolimus administration, and were discrete, ovoid, superficial, well demarcated, and surrounded by an erythematous halo. Their clinical appearance and distribution were similar to that of aphthous stomatitis but inconsistent with CM. Patients with OU were more likely to have nonspecific rashes and acneiform dermatitis but not gastrointestinal AEs.

CONCLUSIONS:

OU associated with mTOR inhibitor therapy differed from CM. Lesions more closely resembled those of aphthous stomatitis. The lack of other gastrointestinal involvement but the presence of a higher incidence of concomitant cutaneous AEs provided additional evidence to suggest a distinction between mIAS and CM. Treatment strategies for aphthous stomatitis may be a rational approach for the prevention and control of mIAS. Cancer 2010. © 2010 American Cancer Society.     

Androgen control of gene expression in the mouse meibomian gland

PURPOSE: In prior work, it has been found that the meibomian gland is an androgen target organ, that androgens modulate lipid production within this tissue, and that androgen deficiency is associated with glandular dysfunction and evaporative dry eye. This study's purpose was to test the hypothesis that the androgen control of the meibomian gland involves the regulation of gene expression. METHODS: Meibomian glands were obtained from orchiectomized mice that were treated with placebo or testosterone for 14 days. Tissues were processed for the analysis of differentially expressed mRNAs by using gene bioarrays, gene chips, and real-time PCR procedures. Bioarray data were analyzed with GeneSifter software (VizX Labs LLC, Seattle, WA). RESULTS: The results show that testosterone influenced the expression of more than 1590 genes in the mouse meibomian gland. This hormone action involved a significant upregulation of 1080 genes (e.g., neuromedin B), and a significant downregulation of 518 genes (e.g., small proline-rich protein 2A). Some of the most significant androgen effects were directed toward stimulation of genes associated with lipid metabolism, sterol biosynthesis, fatty acid metabolism, protein transport, oxidoreductase activity, and peroxisomes. CONCLUSIONS: These findings demonstrate that testosterone regulates the expression of numerous genes in the mouse meibomian gland and that many of these genes are involved in lipid metabolic pathways.     

Young Malaysian children with lower respiratory tract infections show low incidence of chlamydial infection

Objective: The incidence of Chlamydia pneumoniae and Chlamydia trachomatis infection was studied among infants and young children admitted to hospital for the management of lower respiratory tract infections, over a 12 month period.
Methodology: Respiratory secretions were examined for chlamydiae by cell culture, enzyme-linked immunosorbent assay and polymerase chain reaction-enzyme immunoassay. Sera were tested by micro-immunofluorescence for chlamydial IgG, IgM and IgA. Other bacterial and viral pathogens were also looked for by standard cultural and serological methods.
Results: Of 87 patients aged 2 months-3 years, an aetiologic diagnosis was made in 41 (47.1%). C. pneumoniae and C. trachomatis were each detected in 1 (1.2%) of the patients. Among common bacterial pathogens, Haemophilus influenzae (13.8%) and Streptococcus pneumoniae (8.1%) were the most frequently identified. Respiratory viruses and elevated Mycoplasma pneumoniae antibodies were found in 10.3% and 9.1% of patients, respectively.
Conclusion: Chlamydiae are infrequent causes of community-acquired acute lower respiratory tract infections in infants and very young children in Malaysia.