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S T Sonis

Publications and source records attributed to S T Sonis.

At least 19 recordsLinked to original sources
PubMed2006

Subgingival and tongue microbiota during early periodontitis.

Periodontal infections have a microbial etiology. Association of species with early disease would be useful in determining which microbes initiate periodontitis. We hypothesized that the microbiota of subgingival and tongue samples would differ between early periodontitis and health. A cross-sectional evaluation of 141 healthy and early periodontitis adults was performed with the use of oligonucleotide probes and PCR. Most species differed in associations with sample sites; most subgingival species were associated with subgingival samples. Few species were detected more frequently in early periodontitis by DNA probes. Porphyromonas gingivalis and Tannerella forsythia (Tannerella forsythensis) were associated with early periodontitis by direct PCR. In conclusion, the microbiota of tongue samples was less sensitive than that of subgingival samples in detecting periodontal species, and there was overlap in species detected in health and early periodontitis. Detection of periodontal pathogens in early periodontitis suggests an etiology similar to that of more advanced disease.

Adult↗
PubMed2005

Assessment of oral mucositis in clinical trials: impact of training on evaluators in a multi-centre trial.

In the assessment of mucositis, the inter-evaluator variability needs to be minimised and would likely to be best accomplished by training. The aim of this study was to evaluate the effect of training on concordance of evaluators in scoring oral mucositis. The evaluators were informed about the pathobiology and clinical appearance of mucositis and were trained in scoring mucositis according the Oral Mucositis Assessment Scale (OMAS). The effect of the training was evaluated by a pre- and post-training test. Each test consisted of 15 slides depicting oral mucositis. The pre- and post-training scores were compared to the reference standard. During 8 months at 6 meetings, 65 evaluators were trained. The mean percentage correctly scored slides according the OMAS increased significantly between the pre- and post-training test (P<0.001). Training evaluators in scoring oral mucositis has a significant improvement on the outcome of mucositis assessment.

Clinical Competence↗
PubMed2004

The relationship between mucosal cyclooxygenase-2 (COX-2) expression and experimental radiation-induced mucositis.

Although cycloooxygenase-2 (COX-2) is upregulated by factors associated with oral mucositis, its role in the pathogenesis of mucositis has not been studied. We investigated the kinetics of mucosal COX-2 expression following radiation exposure, and assessed its relationship to the development of oral mucositis in an established animal model using immunohistochemical endpoints. While little or no COX-2 expression was observed in unirradiated mucosa or in tissue taken 2 days after radiation, COX-2 expression was dramatic on days 10 and 16, especially in submucosal fibroblasts and endothelium. The kinetics of COX-2 expression paralleled mucositis severity. A burst of angiogenic activity was seen on day 21 following peak COX-2 expression. The kinetics of COX-2 expression relative to mucositis progression suggests that COX-2 is not a primary driver of radiation injury, but instead plays an amplifying role.

Animals↗
PubMed2002

The gene expression sequence of radiated mucosa in an animal mucositis model.

Oral mucositis is a common, dose-limiting, acute toxicity of radiation therapy administered for the treatment of cancers of the head and neck. Accumulating data would suggest that the pathogenesis of mucositis is complex and involves the sequential interaction of all cell types of the oral mucosa, as well as a number of cytokines and elements of the oral environment. While a number of studies have reported on gene expression of particular cell types in response to radiation, the overall response of irradiated mucosa has only been evaluated in a limited way. The present study was undertaken to evaluate the expression of a target group of genes using RNA quantification assays and, more broadly, to assess patterns of mucosal gene expression using DNA microarray hybridization. Our results demonstrate the sequential upregulation of a series of genes that, when taken collectively, suggest an intricate functional interaction.

Animals↗
PubMed2001

Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation.

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients' peak OMAS scores and days with fever (body temperature > 38.0 degrees C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients' peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P <.05) correlated with all of the outcomes of interest except days with fever (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P <.01), (2) a 2.1-fold increase in risk of significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4) 2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001), and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P =.06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Adult↗
PubMed2000

The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy.

BACKGROUND: Epidermal growth factor (EGF) is present in biologic fluids, including saliva, and plays a role in maintenance of the epithelial barrier and in healing of damaged mucosa. The purpose of this study was to assess the relation between salivary EGF and the severity of oral mucositis in patients with carcinoma of the head and neck during radiation therapy. METHODS: Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected prior to radiation and each week during radiation treatment for 11 men and 7 women. Oral mucositis was evaluated using the National Cancer Institute (NCI) scale of 0-4 and the Oral Mucositis Assessment Scale (OMAS), which evaluates the extent of erythema (scale of 0-2) and ulcerations (scale of 0-3) in nine oral sites. The overall OMAS score of 0-45 reflected the mucosal condition. EGF was assayed in the saliva specimens. RESULTS: The total mean radiation dose delivered to the head and neck was 5667 centigrays (cGy) in a mean of 24 fractions. Ulcerative oral mucositis occurred in 94% of patients. The mean OMAS score ranged from 2.83 in the first week of treatment to 14.77 in the fifth week. The mean WRS and WSS volumes decreased significantly from pretreatment to the first week of radiation treatment and then remained stable. A similar pattern was seen for the mean total output of EGF. A significant and negative correlation was found between higher levels of EGF in stimulated saliva and low OMAS score, reflecting less severe erythema and ulceration. A general trend showing that less tissue damage was associated with a higher EGF level in resting saliva also was illustrated. EGF levels were correlated with the OMAS score; however, no correlation was found when assessing the NCI score, which combines tissue damage with function and symptoms in a single score. CONCLUSIONS: Radiation-induced mucositis appeared to be modified by saliva volume, total EGF, and concentration of EGF in the oral environment. Saliva volume and total EGF output decreased significantly in the first weeks of treatment and remained reduced throughout radiation therapy. The findings suggest that higher levels of EGF in saliva, particularly in stimulated saliva, prior to and during radiation treatment may be associated with less severe mucosal damage due to radiation therapy. It is also postulated that human EGF may affect the development and healing of radiation-damaged mucosa.

Adult↗
PubMed2000

Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters.

Oral ulcerative mucositis is a common toxicity associated with drug and radiation therapy for cancer. It impacts on quality of life and economic outcomes, as well as morbidity and mortality. Mucositis is often associated with dose limitations for chemotherapy or is a cause for dose interruption for radiation. The complexity of mucositis as a biological process has only been recently appreciated. It has been suggested that the condition represents a sequential interaction of oral mucosal cells and tissues, pro-inflammatory cytokines and local factors such as saliva and the oral microbiota. The recognition that the pathophysiology of mucositis is a multifactorial process was partially suggested by the observation that interleukin-11 (IL-11), a pleotropic cytokine, favorably altered the course of chemotherapy-induced mucositis in an animal model. In the current study, we evaluated a series of biologic and morphologic outcomes to determine their roles and sequence in the development of experimental radiation-induced mucositis and to evaluate the effects of IL-11 in attenuating them. Our results suggest that IL-11 favorably modulates acute radiation-induced mucositis by attenuating pro-inflammatory cytokine expression. Data are also presented which help define the pathobiological sequence of mucositis.

Animals↗
PubMed1999

Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Mucositis Study Group.

BACKGROUND: An impediment to mucositis research has been the lack of an accepted, validated scoring system. The objective of this study was to design, test, and validate a new scoring system for mucositis that can be used easily, is reproducible, and provides an accurate system for research applications. METHODS: A panel of experts, convened to design an objective, simple, and reproducible assessment tool to evaluate mucositis with specific application to multicenter clinical trials, developed a scale that measured objective and subjective indicators of mucositis. Nine centers participated in the study's validation. Paired investigators at each center evaluated patients receiving chemotherapy or head and neck radiation. Objective measures of mucositis evaluated ulceration/pseudomembrane formation and erythema. Subjective outcomes of mouth pain, ability to swallow, and function were measured. Analgesia use for mouth sensitivity was recorded. RESULTS: One hundred eight chemotherapy and 56 radiation therapy patients were evaluated. Seventy-eight percent of chemotherapy patients and 64% of radiation therapy patients had clinically significant mucositis. Cumulative daily mucositis scores demonstrated a high correlation among observers. Using area under the curve analysis, it was found that for chemotherapy patients, the highest correlations (correlation coefficient > 0.92) occurred for the scores that selected the three highest daily values over the course of mucositis assessment. High interobserver correlations were noted for patients receiving radiation therapy. Objective mucositis scores demonstrated strong correlation with symptoms. CONCLUSIONS: The scoring system evaluated was easily used, showed high interobserver reproducibility, was responsive over time, and measured those elements deemed to be associated with mucositis. The use of concomitant symptomatic measurements appeared to be unnecessary.

Adult↗
PubMed1999

Effect of local application of the antimicrobial peptide IB-367 on the incidence and severity of oral mucositis in hamsters.

OBJECTIVE: The purpose of this animal study was to determine whether IB-367, an antimicrobial peptide, is able to ameliorate oral mucositis by reducing microflora densities on the mucosal surfaces of the mouth. STUDY DESIGN: Oral mucositis was induced in hamsters by intraperitoneal injection of 5-fluorouracil followed by superficial abrasion of the buccal mucosa. A test formulation was applied topically to the buccal mucosa 5 or 6 times per day starting 6 to 8 hours before abrasion. RESULTS: Mucositis scores were significantly lower (P < .05) in hamsters given formulations containing 0.5 or 2.0 mg/mL of IB-367 than in placebo-treated controls. Treatment with IB-367 produced a more than 100-fold reduction in oral microflora densities. In a second experiment, treatment of hamsters with a formulation containing IB-367 at 0.12, 0.5 or 2.0 mg/mL resulted in a dose-dependent reduction in mucositis severity. CONCLUSION: The results indicate that reduction of local microflora densities through use of IB-367 may improve clinical outcomes in patients at risk for the development of oral mucositis.

Animals↗
PubMed1998

The impact of mucositis on alpha-hemolytic streptococcal infection in patients undergoing autologous bone marrow transplantation for hematologic malignancies.

BACKGROUND: Antibacterial prophylaxis with quinolone antibiotics has resulted in an increase in streptococcal infections among bone marrow transplantation (BMT) recipients with myelosuppression. Oral ulceration (mucositis), which frequently occurs as a consequence of chemotherapy, has been implicated as a significant portal of entry for streptococci. The objectives of this study were to confirm the correlation between mucositis and streptococcal bacteremia, determine the risk associated with this correlation, and evaluate the impact of mucositis and streptococcal bacteremia on hospital course and costs associated with autologous BMT. METHODS: This was a retrospective, case-control study in which the charts of autologous BMT recipients treated for hematologic malignancies between 1990 and 1996 were reviewed. Twenty-four patients were identified who met the criteria of autologous BMT; their blood cultures confirmed (x2) alpha-hemolytic streptococcal sepsis. A control group of 45 without positive cultures was matched by gender, age, diagnosis, and treatment to the study group. RESULTS: The results confirm that ulcerative mucositis is a significant risk factor for alpha-hemolytic streptococcal bacteremia among autologous BMT patients. Of the 24 patients with bacteremia, 15 of 24 (62%) had ulcerative mucositis, compared with 16 of 45 (36%) of patients in the control population (P < 0.05). Patients with ulcerative mucositis were found to be three times as likely to develop alpha-hemolytic streptococcal bacteremia as those without ulcerative mucositis (odds ratio=3.02). Both independently and as a cofactor associated with bacteremia, mucositis adversely affected the length of hospital stay (LOS). Of all the patients studied, those with oral ulcerations had a LOS of 34 days, compared with 29 days for patients without oral ulcerations (P < 0.05). Of patients in the study group, those with oral ulcerations stayed in the hospital 6 days longer than patients without oral ulcerations (40 days vs. 34 days, P < 0.05). CONCLUSIONS: Oral ulcerative mucositis is a significant, common, and important risk factor for alpha-hemolytic streptococcal bacteremia in BMT recipients with myelosuppression; it results in longer hospital stay and increased costs.

Adult↗
PubMed1998

Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity.

Mucositis induced by antineoplastic drugs is an important, dose-limiting and costly side effect of cancer therapy. The ulcerative lesions which result are frequent systemic portals of entry for microorganisms which inhabit the mouth and consequently are often sources of systemic infection in the myelosuppressed patient. A number of clinical observations and the inconsistency of responses to a broad range of treatment modalities suggests a physiological complexity to mucositis which has not previously been comprehensively considered. We now propose a hypothesis as to the mechanism by which mucositis develops and resolves, which is based on four phases: an initial inflammatory/vascular phase; an epithelial phase; an ulcerative/bacteriological phase; and a healing phase. The role of cytokines as initiators and ampliers of the process is discussed, as is the potential influence of genetic factors in establishing risk and modifying the course of stomatotoxicity.

Antineoplastic Agents↗
PubMed1998

New frontiers in the management of chemotherapy-induced mucositis.

About one-third of patients undergoing chemotherapy treatment suffer oral mucositis, an inflammatory-like change of the oral mucosa. Severe pseudomembranous/ulcerative mucositis can lead to secondary infection of lesions, sepsis and even cessation of treatment. Patients receiving curative head-neck irradiation are most susceptible and children undergoing chemotherapy are three times more likely to be affected. Mucositis is a costly side-effect of cancer therapy due to the extra time patients spend in hospital and currently there is no consistently effective treatment. Experimental studies with TGF-beta 3, a potent negative regulator of epithelial and haematopoietic stem cell growth, have shown that it is possible to temporarily arrest oral mucosal basal cell proliferation, and could therefore offer a new effective and safe form of preventative intervention for patients about to undergo aggressive regimens of cancer therapy.

Adult↗
PubMed1997

Mitigating effects of interleukin 11 on consecutive courses of 5-fluorouracil-induced ulcerative mucositis in hamsters.

Ulcerative mucositis is a painful, debilitating and dose-limiting toxicity of cancer chemotherapy. Current treatment is largely palliative and no adequate preventive treatment exists. Recently, we reported that recombinant human(rh) interleukin 11 (IL-11) favourably modified the course of mucositis following a single stomatotoxic regimen of 5-fluorouracil in hamsters. Although potentially beneficial, the clinically relevant issue of mucositis and myelosuppression during multicourse chemotherapy treatment was not addressed. The present study was undertaken to evaluate the effect of rhIL-11 on two consecutive courses of mucositis and myelosuppression in hamsters. Ulcerative mucositis was induced using a standardized protocol consisting of 5-fluorouracil (60 mg/kg) on days 1 and 2 followed by superficial irritation of the buccal mucosa on day 4. Animals treated with 100 microg of rhIL-11 for 12 consecutive days following each regimen of chemotherapy experienced a reduction in the incidence, severity, and duration of mucositis, a reduction in weight loss, and less morbidity and mortality relative to control animals. Bone marrow cellularity and function was not adversely affected by rhIL-11 treatment. The present study is consistent with the potential use of rhIL-11 treating patients at risk of developing ulcerative mucositis while undergoing intensive multicourse chemotherapy treatment.

Animals↗
PubMed1997

Transforming growth factor-beta 3 mediated modulation of cell cycling and attenuation of 5-fluorouracil induced oral mucositis.

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which derives from damage to the epithelial cell layer. We have shown that transforming growth factor-beta 3 (TGF-beta 3) negatively regulates epithelial cell proliferation and reduces the incidence of oral mucositis. Here, we report the findings of a large study examining the effects of TGF-beta 3 administration in a hamster model on oral epithelial cell cycling in vivo, on oral mucositis, on weight retention and on survival. Topical application of TGF-beta 3 to the buccal mucosa significantly reduced basal cell proliferation, as measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and DNA ploidy. Administration of topical TGF-beta 3 prior to chemotherapy with 5-fluorouracil (5-FU) significantly reduced the severity of mucositis with respect to time, reduced chemotherapy-associated weight loss and increased survival.

Administration, Topical↗
PubMed1996

Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease.

Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (B10.BR-->CBA/J). Further analysis demonstrated that increased survival in recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone marrow transplantation. These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage.

Adoptive Transfer↗
PubMed1996

Risk factors affecting hospital length of stay in patients with odontogenic maxillofacial infections.

PURPOSE: This study identified potential risk factors associated with increasing hospital length of stay (LOS) in patients with odontogenic maxillofacial infections. PATIENTS AND METHODS: One hundred twenty-eight patients admitted to Brigham and Women's Hospital by the Division of Oral Surgery between October 1, 1984 and March 31, 1995 with a maxillofacial infection of dental origin were retrospectively identified by a medical chart review. Linear regression techniques were used to explain the relationship between patient admission characteristics and LOS. Variables considered included age, gender, infection location, admission white blood count (WBC), admission temperature, antibiotic treatment during hospitalization, attending surgeon, insurance class, operating room use (ORU), and preexisting medical conditions associated with chronic immunosuppression. RESULTS: The following variables were found to significantly increase LOS: ORU (P = .007), preexisting medical conditions (P < .0001), admission temperature (P = .022), and deep infection (P = .063). CONCLUSION: LOS is best predicted on the basis of underlying medical conditions and location of the infection.

Adult↗