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Biomedical subjects

Mark A Reynolds

Publications and source records attributed to Mark A Reynolds.

At least 19 recordsLinked to original sources

Surgical salvage for local and regional recurrence in oral cancer.

PURPOSE: To evaluate local and regional recurrence and the outcomes for salvage surgery in patients for oral cancer. PATIENTS AND METHODS: This study analyzed 354 consecutive patients with oral cancer treated primarily by surgery or surgery combined with adjuvant therapy by 1 surgeon (R.A.O.) between February 1991 and September 2001. RESULTS: Overall recurrence rate was 15.5%; with 5.4% local, 8.5% regional, and 1.4% locoregional. Overall salvage for local recurrence was 52.6% 3-year survival, and statistically significant favorable prognostic factors were salvaged by surgery alone and initial cancer staging of I/II. Overall salvage for regional recurrence was 50%, with recurrence in a previously untreated neck and salvage with radical neck dissection plus radiotherapy giving the best prognosis. No patients with locoregional recurrence were salvaged. CONCLUSIONS: Patients who were stage I/II and were treated initially by surgery alone were the best candidates for salvage if they recurred. Salvage was best achieved with surgery or surgery + adjuvant therapy, and patients recurring within 6 months had a worse survival. Patients with locoregional recurrence or treated with RT +/- chemotherapy alone have negligible survival.

Carcinoma, Squamous Cell↗

Evaluation of the adjunctive benefits of platelet-rich plasma in subantral sinus augmentation.

Subantral sinus augmentation is often necessary to permit placement of endosseous implants. Recent efforts to improve wound healing have focused on autogenous sources of bioactive mediators, such as platelet-rich plasma (PRP), which offer the potential to enhance the biological activity of bone replacement grafts. The purpose of this randomized, single-blinded, controlled study was to compare bone formation after subantral maxillary sinus augmentation with freeze-dried bone allograft (FDBA) plus PRP versus FDBA plus resorbable membrane. Ten patients underwent bilateral maxillary subantral sinus augmentation, with sites within subjects randomized to receive FDBA plus PRP or FDBA plus membrane. Core biopsy specimens were obtained 4.5 to 6 months after the grafting procedure at time of implant placement. Histomorphometric analysis revealed a significantly higher percentage of vital tissue in sinuses after treatment with FDBA and PRP (78.8 +/- 8.3) than with FDBA and membrane (63.0 +/- 15.7). Moreover, the percentage of bone formation in sinuses augmented with the combination of FDBA plus PRP (33.3 +/- 11.3) was nonsignificantly (P </= 0.10) higher than in sinuses grafted with FDBA plus membrane (26.5 +/- 6.8). Residual graft particles constituted a significantly higher percentage of the regenerate in sinuses treated with FDBA plus membrane than in sinuses augmented with FDBA plus PRP (37.0 +/- 15.7) versus (21.2 +/- 8.3, respectively). When comparing the relative proportion of vital bone to residual graft particles, a significant difference also was observed between sinuses treated with FDBA and membrane compared with sinuses augmented with FDBA and PRP (0.98 +/- 0.77 versus 1.82 +/- 0.88, respectively). The results of this study suggest that the combination of FDBA and PRP enhances the rate of formation of bone compared with FDBA and membrane, when used in subantral sinus augmentation. Future research is needed to determine the clinical significance and the cost- and risk-benefit considerations of the approach.

Absorbable Implants↗

Minocycline-associated intra-oral soft-tissue pigmentation: clinicopathologic correlations and review.

BACKGROUND: Intra-oral minocycline staining of alveolar bone and teeth is well-described in the literature. Minocycline-induced discoloration of oral soft tissues is less common and has been often attributed to staining of the underlying bone. AIM: This report documents the clinical and histopathologic features of a case of actual oral soft tissue minocycline-induced pigmentation. The patient, a 45-year-old Caucasian female, presented with pigmentation of the gingiva, lips, and nail beds of recent onset. The past medical history revealed initiation of minocycline therapy 6 months earlier for dermatological concerns. Histopathologic examination of biopsy specimens from the gingiva and lip showed evidence of increased melanin/melanocytes in the epithelium and melanin/melanophages in the connective tissue. A working diagnosis of drug-associated pigmentation was determined and the patient discontinued immediately minocycline therapy. Nine months after cessation of minocycline the patient exhibited a marked reduction in pigmentation. CONCLUSION: Systemic minocycline treatment has the potential to induce significant and esthetically objectionable discoloration of the gingiva and oral mucosa. A brief review of the literature is presented to help understand this uncommon finding that should be included in the differential diagnosis of spontaneous discoloration of intra-oral soft tissues.

Anti-Bacterial Agents↗

Sex differences in temporal summation of pain and aftersensations following repetitive noxious mechanical stimulation.

Several studies demonstrate that women are more sensitive to experimental pain than men. In addition, women exhibit greater temporal summation of heat and mechanically evoked pain. Since temporal summation of pain is centrally mediated, its greater expression in women suggests a central nociceptive hyperexcitability relative to men. The purpose of this study was to pursue this theory, by further assessing sex differences in (1) temporal summation of mechanically evoked pain, and (2) aftersensations following repetitive noxious stimulation. Sixteen series of 10 repetitive, mildly noxious, mechanical stimuli were applied to the fingers of 25 women and 25 age-matched men. The subjects rated the pain intensity and unpleasantness caused by the first, fifth and tenth stimulus in the series, as well as their aftersensations 15 s and 1 min following the end of stimulation. Data were analyzed by three-way repeated-measures analysis of variance. Pain and unpleasantness ratings increased with repetition of stimulation (P<0.0001). Temporal summation of pain intensity and unpleasantness ratings were more pronounced in women than men (P<0.0001). In addition, significant temporal summation occurred only with 2 s interstimulus interval for men (P<0.0005) but with 2 and 5 s interstimulus interval for women (P<0.0001). Moreover, women provided greater ratings for the intensity and the unpleasantness of aftersensations (P<0.0005) and reported painful aftersensations at greater frequency (P<0.05) Greater temporal summation of pain and aftersensations in women suggests that their central processing of nociceptive input may be more easily upregulated into pathological hyperexcitability, possibly accounting for the higher prevalence of various chronic pain conditions among women.

Adult↗

Clinical evaluation of calcium sulfate in combination with demineralized freeze-dried bone allograft for the treatment of human intraosseous defects.

BACKGROUND: Medical-grade calcium sulfate (CS) is a biocompatible, bioabsorbable, and clinically versatile ceramic for use in bone repair. This study compared the clinical efficacy of a combination of calcium sulfate dihydrate, as a binder and barrier, and demineralized freeze-dried bone allograft (DFDBA) to polytetrafluoroethylene (ePTFE) and DFDBA for the treatment of human periodontal defects. METHODS: Two intrabony defects were compared in each of 19 patients with chronic periodontitis. After initial preparation, full-thickness mucoperiosteal flaps were elevated, osseous defects debrided, and the roots prepared (ultrasonic, hand curets, and tetracycline conditioning). Defects were randomly treated with either a combination graft of DFDBA with CS (4:1) covered by a CS barrier or with DFDBA and fitted with an ePTFE barrier. Flaps were coronally positioned to obtain primary closure. Clinical soft tissue measurements were recorded at 6 months, and all study sites were surgically reentered for evaluation. RESULTS: The mean presurgical measurements for defects randomized to the CS and ePTFE treatments, respectively, were similar for attachment level (AL; 6.2 +/- 1.8 mm and 6.1 +/- 1.7 mm), probing depth (PD; 6.3 +/- 1.1 mm and 6.2 +/- 1.1 mm), and gingival recession (0.1 +/- 1.9 mm and 0.2 +/- 1.4 mm). Defects treated with CS or ePTFE demonstrated statistically significant (P < or = 0.0001) reductions in mean PD (2.7 +/- 1.4 mm and 3.4 +/- 1.3 mm, respectively) and gains in mean AL (1.8 +/- 1.5 mm and 1.7 +/- 1.4 mm, respectively). Recession increased by 0.8 +/- 1.4 mm at CS sites and 1.6 +/- 1.7 mm at ePTFE-treated sites (P < or = 0.05). Pretreatment mean defect depths were 4.1 +/- 1.0 mm and 3.7 +/- 1.0 mm for CS and ePTFE sites, respectively. Reentry evaluations revealed a mean defect fill of 2.7 +/- 1.5 mm and 2.5 +/- 0.9 mm for the CS and ePTFE sites, respectively, with a corresponding mean defect resolution of 80.3 +/- 18.7% and 76.7 +/- 18.5%. The CS and ePTFE sites did not differ significantly in mean defect fill or defect resolution. CONCLUSIONS: The results of this study indicate that calcium sulfate, when used as a binder and barrier in combination with DFDBA, supports significant clinical improvement in intrabony defects, as evidenced by reductions in probing depth, gains in clinical attachment level, and defect fill and resolution. Calcium sulfate represents an important alternative to non-resorbable ePTFE barriers in combination with DFDBA for the treatment of intrabony defects.

Adult↗

Estrogen suppression induces papillary gingival overgrowth in pregnant baboons.

BACKGROUND: Alterations in sex steroids during pregnancy are associated with the development and exacerbation of reactive lesions involving the gingiva. Currently, few experimental animal models similar to humans are available to examine regulatory pathways involving sex steroids and the periodontium. METHODS: In the present study, we used the baboon as a novel experimental model for the study of the regulatory actions of estrogen on the periodontium during pregnancy. Pregnant baboons (N = 5) were administered the potent, highly specific aromatase inhibitor CGS 20267 (2 mg/day subcutaneously) daily on days 60 through 165 of gestation (term = 184). Untreated females (N = 10) and females (5) concomitantly administered aromatase inhibitor and estradiol benzoate (2.0 mg/day each subcutaneously) served as controls. Gingival biopsies were taken between days 145 and 165 of gestation. RESULTS: Administration of CGS 20267 in all females suppressed maternal serum concentrations of estradiol by 95% and induced the development of an exuberant papillomatous enlargement of the gingiva by gestational day 110, with the most prominent development involving the labial aspects of the anterior sextants. None of the untreated pregnant controls or females concomitantly administered aromatase inhibitor and estradiol benzoate developed gingival overgrowth. Thus, estradiol alone prevented the onset of gingival overgrowth induced by estrogen suppression. In all baboons, discontinuation of the aromatase inhibitor at time of cesarean section resulted in spontaneous regression and resolution of the papillomatous hyperplasia within 4 to 6 weeks. Clinically, the gingival papillary overgrowth was erythematous and edematous, with a propensity toward spontaneous subgingival hemorrhage. Histologically, the biopsy specimens demonstrated hyperplasia of the epithelium typified by mild hyperkeratosis, acanthosis, and elongation and isolated anastamoses of rete ridges. Subjacent to the intact epithelium was a loose connective tissue stroma with isolated areas of inflammatory cell infiltrate. Special stains verified the presence of isolated bacterial biofilms; however, no evidence of fungal filaments was present. Histological features suggestive of viral infection were notably absent in the epithelium. No evidence of viral particles or capsids was identified using transmission electron microscopy. Reverse transcription polymerase chain reaction analysis, using a panel of degenerate primers, was negative for papilloma family viruses. CONCLUSIONS: These results are consistent with a significant role for estrogen during primate pregnancy in the regulation of cellular proliferation and differentiation within the gingiva. The baboon represents an important experimental model for studying the regulatory actions of estrogen on the periodontium during pregnancy.

Animals↗

Evidence for up-regulated central nociceptive processing in patients with masticatory myofascial pain.

AIMS: Previous work suggests that hyperexcitability of central nociceptive neurons may play a role in the pain of temporomandibular disorders (TMD). The aim of this study was to test this theory by assessing differences, between myalgic TMD patients and pain-free controls, in temporal summation of mechanically evoked pain and aftersensations following repetitive noxious stimulation. METHODS: Sixteen series of 10 repetitive, mildly noxious mechanical stimuli were applied to the fingers of 25 female TMD patients with masticatory myofascial pain and 25 age-matched, pain-free female subjects. All subjects rated the pain intensity and unpleasantness evoked by the first, fifth, and tenth stimuli in the series and their aftersensations at 15 seconds and 1 minute following the last stimulus. Data were analyzed by 3-way repeated-measures analysis of variance. RESULTS: Pain and unpleasantness ratings increased with repetition of the stimulation (P < .0001). In addition, there was a significant trial number x group interaction for the pain intensity ratings, such that TMD patients provided higher ratings than controls for the tenth stimulus (P < .001). The increase in unpleasantness ratings with repetitive stimulation was also higher for the patient group (P < .0001). Moreover, TMD patients rated the intensity of aftersensations as higher (P < .005) and reported painful aftersensations at significantly greater frequency (P < .05). CONCLUSION: A generalized hyperexcitability of central nociceptive processing in this TMD patient group is indicated by their more pronounced temporal summation of pain and greater aftersensations following repetitive noxious digital stimulation versus controls. Such hyperexcitability may contribute to the pathophysiology of TMD pain.

Adult↗

Carcinosarcoma of the maxilla in a squirrel monkey (Saimiri sciureus).

We present the first, to our knowledge, described case of carcinosarcoma of the maxilla in a squirrel monkey. Carcinosarcomas are rare tumors of the upper aerodigestive tract, and consist of carcinomatous and sarcomatous tissue. Histologic analysis revealed a neoplasm composed of an adenocarcinomatous component (epithelial element) and a mesenchymal component (sarcomatous element). Metastatic growth was documented in the lung tissue and the submandibular lymph node. The histolopathologic findings, the pattern of metastasis, and the clinical progression closely resembled those of carcinosarcoma involving salivary glands in humans.

Animals↗

Immunohistochemical expression of angiogenesis-related markers in oral squamous cell carcinomas with multiple metastatic lymph nodes.

The aim of this study was to evaluate the histopathologic features and the expression of angiogenesis-related markers in primary tumors and metastatic lymph nodes of oral squamous cell carcinomas (SCCs) with multiple lymph node involvement in comparison with oral SCCs without nodal metastasis. The protein levels of the angiogenesis inhibitor endostatin, as well as those of the related molecules collagen XVIII, collagen-binding protein (CBP) 2/heat shock protein (HSP) 47, and cathepsin L, were evaluated by immunohistochemical analysis. Compared with nonmetastatic cases, primary tumors of the metastatic group exhibited significantly decreased protein levels of endostatin and its precursor collagen XVIII. Comparison between primary tumors and positive nodes of the metastatic cases revealed decreased expression of collagen XVIII and CBP2/HSP47 in metastases. Angiogenesis is essential for tumor growth and metastasis; accordingly, the observed differences in the immunohistochemical expression of angiogenesis-related proteins in oral SCC with multiple lymph node involvement may provide an explanation for the increased metastatic potential of these tumors.

Adult↗

Early biomarkers of stroke.

BACKGROUND: The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (<33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests. METHODS: ELISAs for >50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke. RESULTS: The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset. CONCLUSION: A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.

Acute Disease↗

Formation of mucogingival defects associated with intraoral and perioral piercing: case reports.

BACKGROUND: The authors provide clinical findings in five patients wearing oral jewelry to illustrate the risks of experiencing periodontal injury associated with body piercing involving intraoral and perioral sites. They also present a literature review of other adverse dental and medical consequences attributed to oral piercing. CASE DESCRIPTIONS: Five young adult patients with tongue and lip piercing sought dental care. Each patient exhibited some degree of gingival recession and mucogingival defects in proximity of their oral jewelry. Three of these patients had probing depths ranging from 5 to 8 millimeters in the affected areas. CLINICAL IMPLICATIONS: Intraoral and perioral jewelry may be associated with the development of significant mucogingival deformities. Because severe attachment loss can develop even when gingival recession is minimal, it is critical that patients with oral piercing routinely undergo comprehensive periodontal assessment. The authors urge clinicians to educate patients about the potential risks regarding the practice of oral piercing.

Adult↗

The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review.

BACKGROUND: Bone replacement grafts (BRG) are widely used in the treatment of periodontal osseous defects; however, the clinical benefits of this therapeutic practice require further clarification through a systematic review of randomized controlled studies. RATIONALE: The purpose of this systematic review is to access the efficacy of bone replacement grafts in proving demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone. FOCUSED QUESTION: What is the effect of bone replacement grafts compared to other interventions on clinical, radiographic, adverse, and patient-centered outcomes in patients with periodontal osseous defects? SEARCH PROTOCOL: The computerized bibliographical databases MEDLINE and EMBASE were searched from 1966 and 1974, respectively, to October 2002 for randomized controlled studies in which bone replacement grafts were compared to other surgical interventions in the treatment of periodontal osseous defects. The search strategy included screening of review articles and reference lists of retrieved articles as well as hand searches of selected journals. INCLUSION CRITERIA: All searches were limited to human studies in English language publications. EXCLUSION CRITERIA: Non-randomized observational studies (e.g., case reports, case series), publications providing summary statistics without variance estimates or data to permit computation, and studies without BRG intervention alone were excluded. DATA COLLECTION AND ANALYSIS: The therapeutic endpoints examined included changes in bone level, clinical attachment level, probing depth, gingival recession, and crestal resorption. For purposes of meta-analysis, change in bone level (bone fill) was used as the primary outcome measure, measured upon surgical re-entry or transgingival probing (sounding). MAIN RESULTS: 1. Forty-nine controlled studies met eligibility criteria and provided clinical outcome data on intrabony defects following grafting procedures. 2. Seventeen studies provided clinical outcome data on BRG materials for the treatment of furcation defects. REVIEWERS' CONCLUSIONS: 1. With respect to the treatment of intrabony defects, the results of meta-analysis supported the following conclusions: 1) bone grafts increase bone level, reduce crestal bone loss, increase clinical attachment level, and reduce probing depth compared to open flap debridement (OFD) procedures; 2) No differences in clinical outcome measures emerge between particulate bone allograft and calcium phosphate (hydroxyapatite) ceramic grafts; and 3) bone grafts in combination with barrier membranes increase clinical attachment level and reduce probing depth compared to graft alone. 2. With respect to the treatment of furcation defects, 15 controlled studies provided data on clinical outcomes. Insufficient studies of comparable design were available to submit data to meta-analysis. Nonetheless, outcome data from these studies generally indicated positive clinical benefits with the use of grafts in the treatment of Class II furcations. 3. With respect to histological outcome parameters, 2 randomized controlled studies provide evidence that demineralized freeze-dried bone allograft (DFDBA) supports the formation of a new attachment apparatus in intrabony defects, whereas OFD results in periodontal repair characterized primarily by the formation of a long junctional epithelial attachment. Multiple observational studies provide consistent histological evidence that autogenous and demineralized allogeneic bone grafts support the formation of new attachment. Limited data also suggest that xenogenic bone grafts can support the formation of a new attachment apparatus. In contrast, essentially all available data indicate that alloplastic grafts support periodontal repair rather than regeneration. 4. The results of this systematic review indicate that bone replacement grafts provide demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone.

Alveolar Bone Loss↗

The segmental osteotomy in the management of malposed implants: a case report and literature review.

BACKGROUND: The segmental osteotomy provides an important treatment approach for the correction of skeletal-dental malocclusions that would otherwise be unmanageable with conventional orthodontic care. The combined use of orthodontics and orthognathic surgery also has been adapted for use in the correction of developmental and traumatic deformities. Severely malpositioned implant fixtures may not permit restorative correction even with custom prosthetic appliances. As an alternative to implant removal, which can be associated with significant alveolar destruction, orthognathic surgery may offer a treatment modality to improve fixture alignment, thereby enabling a more favorable esthetic and functional prosthesis. This paper presents a case report and review of the segmental osteotomy procedure. METHODS: A 32-year-old female with congenitally missing maxillary lateral incisors underwent implant surgery for prosthetic replacement of these teeth. Due to severe labial positioning of the implant fixtures, acceptable prosthetic treatment was not possible. A segmental osteotomy procedure was used to reposition the implants. The implants were splinted using a ridged interim suprastructure during the 4-month healing period. An occlusal appliance also was worn during the initial 8 weeks of this healing period. RESULTS: The surgical procedure permitted intrusion and palatal repositioning of the implants. Healing proceeded with no untoward effects. Clinical findings at second-stage surgery were consistent with complete osseous repair and integration of the fixtures. Successful prosthetic treatment was subsequently completed for the patient. CONCLUSION: The segmental osteotomy may provide an alternative treatment to the removal of severely malposed implants or their compromised prosthetic restoration.

Adult↗

Factors influencing the outcome of regenerative therapy in mandibular Class II furcations: Part I.

BACKGROUND: Factors influencing the outcome of regenerative therapy of Class II furcations are incompletely and poorly understood. The purpose of this 24-month prospective study was to examine the relationship of patient-, site-, and treatment-related factors to the clinical closure of randomly selected mandibular Class II furcations. Results of therapy were evaluated at 1 and 2 years postoperatively. One-year outcome data are presented in this report. METHODS: A total of 43 otherwise healthy individuals with chronic periodontitis (26 male, 17 female), 36 to 70 years of age, completed the 12-month evaluation of the study. Entry criteria included clinical and radiographic evidence of two or more mandibular facial Class II furcation defects (> or = 3 mm horizontal probing depth). Surgical therapy was completed by four periodontists (two each) in either a university clinic or private practice. Each patient contributed two furcation defects that were treated by combination therapy using an expanded polytetrafluoroethylene (ePTFE) membrane and demineralized freeze-dried bone allograft (DFDBA). Clinical measurements included a gingival index, plaque index, mobility, and, referencing an occlusal stent, probing depth (PD), probing attachment level-vertical (PAL-V), and probing attachment level-horizontal (PAL-H). Multiple linear measurements were recorded for each site clinically and after surgical debridement to characterize defect morphology, root configuration, and barrier placement. Defect volume was computed mathematically. Postsurgical maintenance care was provided at 1 to 2, 4, 6, and 8 weeks, and then biweekly until 3 months, with subsequent supportive periodontal maintenance visits at 3-month intervals. The clinical status of the furcation (open or closed), measured by a non-treating periodontist at 1 and 2 years, was the primary outcome measure. The association of patient-related factors (e.g., smoking), site-related factors (e.g., root configuration and defect morphology), and treatment-related factors (e.g., membrane exposure) to clinical status of furcations was assessed using random effects hierarchical logistic regression analysis, controlling for design and demographic variables. Non-parametric analysis was used for specific group comparisons. RESULTS: Complete clinical closure was achieved in 74% of all sites. Of the residual furcation defects, 68% were reduced to Class I. No defects progressed to Class III. Significant improvements in mean PD and PAL-V were obtained following surgical therapy. Although the proportion of sites demonstrating complete furcation closure was comparable for smokers and non-smokers, the proportion of Class II residual defects was significantly higher among smokers than non-smokers (62.5% versus 14.3%, respectively). Increases in presurgical PAL-H were associated with monotonic decreases in the percentage of sites demonstrating complete clinical closure, with only 53% of lesions > or = 5 mm responding with complete closure. Similarly, significant reductions in the frequency of clinical closure were associated with increases in the distance between the roof of furcation and crest of bone, roof of furcation and base of defect, depth of horizontal defect, and divergence of roots at the crest of bone. CONCLUSIONS: The successful clinical closure of Class II furcations was achievable at 1 year following combination therapy with an ePTFE membrane and DFDBA. The highest frequency of clinical furcation closure was observed in early Class II defects. Furcations with vertical or horizontal bone loss of 5 mm or greater responded with the lowest frequency of complete clinical closure. Nevertheless, complete furcation closure was achievable in 50% of molars with extensive bone loss. Also, 15 out of 22 (68%) of all residual defects were reduced to Class I and only seven (8%) failed to improve, demonstrating that successful clinical resolution of advanced defects remains an attainable goal.

Adult↗

PPARgamma-mediated antineoplastic effect of NSAID sulindac on human oral squamous carcinoma cells.

There is strong evidence that nonsteroidal antiinflammatory drug (NSAID) sulindac may exert a significant antineoplastic effect. The purpose of our study was to explore the effects of sulindac on human oral squamous cell carcinoma (SCCa) cells and to elucidate the underlying molecular mechanisms. The changes that sulindac treatment induced on growth, apoptosis and cell cycle distribution of human oral SCCa cell lines were assessed by cell growth and flow cytometry experiments. Utilizing quantitative RT-PCR and immunocytochemistry, we determined the effect of sulindac treatment on mRNA and protein expression of different sulindac's targets. Also, PPARgamma expression was selectively targeted by antisense oligonucleotide treatment. Both sulfide and sulfone metabolites of sulindac, which differ in the ability to cause COX-2 inhibition, induced a significant dose- and time-dependent cell growth reduction accompanied by increase in apoptosis without concomitant cell cycle arrest. Sulindac treatment also caused upregulation of the protein and mRNA expression levels of COX-2 and PPARs. Treatment with antisense PPARgamma oligonucleotides abolished sulindac's growth inhibitory effect. Our results are consistent with a significant growth inhibitory effect of NSAID sulindac on human oral SCCa cells, which is mediated, at least partially, through induction of apoptosis. We suggest that upregulation of PPARgamma expression and activation may be, at least partially, responsible for sulindac's antiproliferative effect.

Anti-Inflammatory Agents, Non-Steroidal↗

Microarray technology GEM microarrays and drug discovery.

Incyte Genomics' GEM Gene Expression Microarray is a proven genomics tool used by a large number of pharmaceutical companies to speed up the drug discovery and development process. The development and integration of this technology, together with Incyte's sequence databases and clone resources, have resulted in GEM microarrays that span approximately 60,000 human genes as well as approximately 60,000 plant, rat, mouse, yeast, and bacterial genes. The technology underlying the use of these arrays and their application to the drug discovery process is highlighted.

Drug Design↗

Biomarkers predictive of lymph node metastases in oral squamous cell carcinoma.

PURPOSE: The ability of oral squamous cell carcinoma to metastasize to lymph nodes does not always show a relationship with clinical staging. The aim of this study was to attempt to define a trend for predictive histopathologic and/or molecular biomarkers in the development of nodal metastasis by analyzing 2 clinically extreme groups. PATIENTS AND METHODS: Patients with small primary tumors (T1, T2) with lymph node metastasis and patients with large primary tumors (T3, T4) without metastatic disease were identified among 315 consecutive cases of primary oral squamous cell carcinoma. Group comparisons were made with use of a Mann-Whitney test, and associations among the variables were assessed with nonparametric and parametric correlational analyses. RESULTS: The degree of keratinization was significantly less in primary tumors with lymph node metastasis (P < or = .01). The degree of keratinization was significantly associated with nuclear pleomorphism (P =.02), number of mitoses (P =.02), stage of invasion (P =.002), and p53 expression (P =.04), independent of clinical stage of the tumor. Other microscopic features and immunohistochemical markers did not differ significantly between the groups (P >.05). CONCLUSION: These data indicate that there still is no single predictive parameter superior to the degree of keratinization to identify patients at risk for the development of regional metastasis.

Adult↗