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Biomedical subjects

Mark S Chambers

Publications and source records attributed to Mark S Chambers.

At least 19 recordsLinked to original sources

Radiation-induced xerostomia.

BACKGROUND: Radiation-induced xerostomia is a frequent and usually permanent side effect of radiation therapy for head and neck cancer. We summarize recent developments in the prevention and treatment of radiation-induced xerostomia. METHODS: The Medline database was searched for articles published within the past 10 years on the prevention and treatment of postirradiation xerostomia. Proceedings of recent important national meetings and government Web registries of clinical trials and therapeutic agents were also consulted. Priority was given to randomized controlled trials but, because of the scarcity of such trials, small open trials were included in this review. No other predetermined selection criteria were used, although articles exploring the effects of xerostomia and its treatment on quality of life were considered of special interest. RESULTS: A variety of preventive approaches for postirradiation xerostomia exist, involving more conformal radiation delivery technology, radioprotective agents, and even preirradiation surgical techniques. Therapeutic interventions include supportive care, saliva supplementation, and the use of pro-cholinergic salivary secretagogues. CONCLUSIONS: Radiation-induced xerostomia constitutes a significant morbidity after orofacial irradiation. Careful preventive techniques, meticulous supportive care, and new preventive and therapeutic agents may prove useful in combination.

Animals↗

Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 1: Fluorides.

Radiation-induced xerostomia results in significant changes in the oral cavity particularly oral microbial changes, which include a marked increase in the number of cariogenic organisms, notably Streptococcus mutans and lactobacillus species. This loss of the capacity to secrete saliva creates or promotes the rapid onset and progression of rampant dental caries. In this 2-part series, the benefit of fluoride in reducing caries activity is presented. Part 1 discusses the historical and currently available fluoride preparations and Part 2 presents data of a recently completed trial investigating the benefit of an intraoral sodium fluoride releasing system.

Anti-Bacterial Agents↗

Clinical evaluation of the intraoral fluoride releasing system in radiation-induced xerostomic subjects. Part 2: Phase I study.

Radiation-induced xerostomia can result in the rapid onset and progression of dental caries in head and neck cancer patients. Topically applied fluorides have been successfully used to inhibit the formation of dental caries in this population. However, because intensive daily self-application is required, compliance is an issue. The intraoral fluoride-releasing system (IFRS) containing a sodium fluoride core is a newly developed, sustained-release, passive drug delivery system that does not require patient involvement except for periodic replacement, thus reducing the effect of patient compliance on its effectiveness in dental caries prevention. Twenty-two head and neck cancer patients from U. T. M. D. Anderson Cancer Center, with radiation-induced xerostomia, were entered into a pilot study to contrast the daily home use of a 0.4% stannous fluoride-gel-containing tray (control group) to IFRS (study group) with respect to tolerability and adherence, and to obtain information on relative caries preventive efficacy. Participants were stratified on the basis of radiation exposure and randomly assigned to treatment with either IFRS or stannous fluoride gel. Patients in both groups were fitted with two IFRS retainers and also were instructed to use a 1100-ppm fluoride conventional sodium fluoride dentifrice twice daily. The study was conducted as a single-blinded, parallel-cell trial. Pre-existing carious lesions were restored prior to the beginning of the study. The efficacy variable was determined by the mean number of new or recurrent decayed surfaces. Patients were examined for caries 4, 8, 12, 24, 36, and 48 weeks after initiation of treatment. Reports of adverse reactions were based on information volunteered by patients and that were elicited during interviews. At baseline, the resting and stimulated salivary flow rates (g/5min) were significantly greater in the control group than in the study group (p<0.05). Patients in the control group had received significantly more radiation than those in the test group (68Gy vs. 60Gy; p=0.047). No marked differences in follow-up new and recurrent caries were found between the stannous fluoride gel control and IFRS groups during the study period. The rate of new or recurrent carious lesions in the group treated with the fluoride gel was slightly lower than in the IFRS group, based on carious lesions at the baseline examination (Poisson mean number of new or recurrent carious lesions for the control group=0.55 per year vs. 0.83 per year for the study group, p=0.705; odds ratio of the occurrence of any new or recurrent caries during follow-up for control group vs. the study group=0.80; p=0.781). This pilot study revealed that the IFRS was well-tolerated and safe in this study population associated with minimal complications during the duration of this study and was comparable in efficacy to a SnF(2) gel in preventing caries development. The IFRS provided similar rates of control for caries formation to a fluoride-gel-containing tray. The IFRS is designed to release a daily dose of 0.12mg of sodium fluoride, which can be evenly distributed throughout the oral cavity for a single application of 4 months. It would be more convenient than the daily home application of a tray of 0.4% stannous fluoride or 1.1% sodium fluoride gel, and avoids the problem of variable patient compliance.

Administration, Topical↗

Multiple regions-of-interest analysis of setup uncertainties for head-and-neck cancer radiotherapy.

PURPOSE: To analyze three-dimensional setup uncertainties for multiple regions of interest (ROIs) in head-and-neck region. METHODS AND MATERIALS: In-room computed tomography (CT) scans were acquired using a CT-on-rails system for 14 patients. Three separate bony ROIs were defined: C2 and C6 vertebral bodies and the palatine process of the maxilla. Translational shifts of 3 ROIs were calculated relative to the marked isocenter on the immobilization mask. RESULTS: The shifts for all 3 ROIs were highly correlated. However, noticeable differences on the order of 2-6 mm existed between any 2 ROIs, indicating the flexibility and/or rotational effect in the head-and-neck region. The palatine process of the maxilla had the smallest right-left shifts because of the tight lateral fit in the face mask, but the largest superior-inferior movement because of in-plane rotation and variations in jaw positions. The neck region (C6) had the largest right-left shifts. The positioning mouthpiece was found effective in reducing variations in the superior-inferior direction. There was no statistically significant improvement for using the S-board (8 out of 14 patients) vs. the short face mask. CONCLUSIONS: We found variability in setup corrections for different regions of head-and-neck anatomy. These relative positional variations should be considered when making setup corrections or designing treatment margins.

Algorithms↗

How to reduce radiation-related toxicity in patients with cancer of the head and neck.

Radiation for head and neck cancers is often curative, but high doses are used. Normal tissues, including mucosa, salivary glands, and muscles, are exposed to these high doses, resulting in severe mucositis, xerostomia, and dysphagia. Efforts to minimize toxicity have involved advances in radiation physics and development of pharmacologic agents. Radiation techniques include conformal and intensity-modulated therapy, which minimizes dose to normal tissues while delivering high doses to tumor targets. Drugs used to prevent mucositis have targeted infection, but recently interest has been shown in the use of growth factors. Cholinergic agonists and cytoprotective agents, specifically amifostine, can address xerostomia. Involvement of speech pathologists in evaluation and treatment of patients with dysphagia can minimize swallowing difficulties and identify the tissues most responsible for swallowing. Minimizing radiation dose to these tissues may lower the incidence of radiation-induced dysphagia.

Amifostine↗

Interactions of pigments and opacifiers on color stability of MDX4-4210/type A maxillofacial elastomers subjected to artificial aging.

STATEMENT OF PROBLEM: The color instability and degradation of maxillofacial elastomers limit the function and cosmetic quality of facial prostheses. PURPOSE: The purpose of this study was to measure the interactions of oil pigments plus dry earth opacifiers at 5%, 10%, and 15% by volume in stabilizing the color of MDX4-4210/type A silicone elastomers before and after artificial aging. MATERIAL AND METHODS: In the first part of the study, each of 5 opacifiers (Georgia kaolin powder neutral, kaolin powder calcined, Artskin white, dry pigment titanium (Ti) white, or Ti white artists' oil color) at 10% concentrations were combined with each of 5 oil pigment types (no pigment, cadmium-barium red deep, yellow ochre, burnt sienna, or a mixture of the 3 pigments), for a total of 25 experimental groups of elastomers. In the second part of the study, 50 experimental groups of elastomers were made by combining 1 of 5 opacifiers at 5% and 15% concentrations with 1 of 5 oil pigments as in Part 1. Five specimens of each elastomer were tested, for a total of 375 specimens. In each part of the study, all specimens were aged in an artificial aging chamber. CIE L*a*b* values were measured by a spectrophotometer. The color differences (DeltaE*) were subjected to repeated-measures analysis of variance. Mean values were compared by Tukey-Kramer intervals (alpha = .05). RESULTS: In Part 1, when the opacifiers were tested at 10% concentration, Ti white oil color had the most color change, and dry pigment Ti white had the least; all other opacifiers were not significantly different from each other. In Part 2, at 5%, Ti white oil color had the most color change; all other opacifiers were not significantly different from the others. At 15%, Ti white oil color again had the most color change, followed by Artskin white, kaolin powder calcined, and Georgia kaolin; Ti white dry earth pigment had the least color change. Overall, 5% Artskin white had less color change than the 15%, whereas 15% dry pigment Ti white had less color change than the 5% (P < .001). The 5% and 15% of other opacifiers were not significantly different. CONCLUSIONS: At all 3 concentrations, oil pigments mixed with opacifiers helped protect the MDX4-4210/type A silicone elastomer from color degradation over time. Dry pigment Ti white remained the most color stable over time, followed by the pigments mixed with kaolin powder calcined, Georgia kaolin, Artskin white, and Ti white artists' oil color.

Barium Sulfate↗

Stent fabrication for graft immobilization following wide surgical excision of myofibroblastic sarcoma of the buccal mucosa: a clinical report.

Sarcomas of the head and neck are rare tumors derived from cells of mesenchymal origin. This article briefly discusses the epidemiology, etiology, and classification of head and neck sarcomas. Emphasis is placed on myofibrosarcoma, a malignant tumor of the myofibroblasts. Histologic criteria, prognostic factors, and the multidisciplinary management of these tumors are reviewed. A situation of a surgically excised myofibrosarcoma of the buccal mucosa is reported. In this patient, a stent was fabricated to stabilize a split-thickness skin graft used for the buccal mucosa reconstruction.

Adult↗

Intensity-modulated radiation therapy and xerostomia.

Conformal radiation with intensity-modulated radiation therapy, IMRT, is a radiation technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. The reduction of xerostomia may be achieved by sparing the salivary glands on the noninvolved oral cavity and keeping the mean parotid gland dose of < 26-30 Gy if the treatment of disease is not compromised and parotid function preservation is desired.

Head and Neck Neoplasms↗

Pharmacokinetics and metabolism studies on (3-tert-butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy) pyrazolo[1,5-d][1,2,4]triazine, a functionally selective GABA(A) alpha5 inverse agonist for cognitive dysfunction.

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (1) was recently identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors and enhances performance in animal models of cognition. The routes of metabolism of this compound in vivo in rat have been well characterised, the identities of the major metabolites are confirmed by synthesis and their biological profiles were evaluated. An unusual oxidation of the pyrazolo[1,5-d][1,2,4]triazine core to the corresponding pyrazolo[1,5-d][1,2,4]triazin-4(5H)-one scaffold by aldehyde oxidase has been observed.

Animals↗

Intensity-modulated radiotherapy: is xerostomia still prevalent?

Conformal radiation with intensity-modulated radiotherapy (IMRT) is a technique that potentially can minimize the dose to salivary glands and thereby decrease the incidence of xerostomia. Precise target determination and delineation is most important when using salivary gland-sparing techniques of IMRT. Reduction of xerostomia can be achieved by sparing the salivary glands on the uninvolved oral cavity and keeping the mean parotid gland dose of less than 26 to 30 Gy as a planning criterion if the treatment of disease is not compromised and parotid function preservation is desired.

Carcinoma, Squamous Cell↗

Mutans streptococci in xerostomic cancer patients after pilocarpine therapy: a pilot study.

OBJECTIVES: Opiod- and/or radiation-induced xerostomia in cancer patients is frequently associated with elevated levels of cariogenic mutans streptococci (MS). STUDY DESIGN: In a single-center, single blind 8-week clinical trial at The University of Texas M. D. Anderson Cancer Center, and from an initial sample of 32 patients, we evaluated MS counts in 28 cancer patients receiving chronic analgesic treatment for cancer pain. All patients received escalating doses of pilocarpine (Salagen) tablets, either 2.5 mg to 5 mg or 5 mg to 7.5 mg qid for 6 weeks, followed by placebo qid for a 2-week washout period. Whole resting saliva flow rates (g/5 min) and MS counts were evaluated at pretreatment, 3 weeks, 6 weeks, and 8 weeks. MS samples were obtained by 5-mL saline rinse (15 sec) at each visit prior to sialometry. RESULTS: In 19 patients (59%), MS counts exceeded 10(5) CFU/mL. At the end of the 6-week trial, 96% of patients showed a positive response to pilocarpine following a 30-minute postdosing evaluation (P=.001). MS counts were lower in 17 patients, higher in 6 patients, and nondetectable before and after pilocarpine in 5 patients (P=.03). CONCLUSION: The reduced MS counts associated with improved saliva flow rates following pilocarpine therapy in this short-term pilot study are encouraging, but further investigation in a larger group of patients over a longer study period is indicated.

Analgesics, Opioid↗

Facial prosthetic rehabilitation: preprosthetic surgical techniques and biomaterials.

PURPOSE OF REVIEW: Attention to detail ensuring a successful facial prosthetic rehabilitation must be considered a priority at the time of presurgery, surgery, and at every stage in fabricating the prosthesis. Teamwork between the surgeon and maxillofacial prosthodontist will ensure an optimal surgical preparation and definitive prosthesis. RECENT FINDINGS: Evidence of interaction between team members can most certainly be encouraging to the patient. During the prosthetic phase of treatment, focusing on tissue assessment, impression making, sculpting, mold fabrication, familiarity with materials, appreciation of color, delivery of instructions, and patient education will ensure a satisfactory outcome. With the desire, determination, and encouragement from the restorative team to make the most of this artificial replacement, a patient can have a higher quality of life and a more normalized lifestyle. SUMMARY: This review presents current concepts regarding facial prosthetic rehabilitation of patients with head and neck cancer and facial prosthetic biomaterials.

Biocompatible Materials↗

Period between completion of radiation therapy and prosthetic rehabilitation in edentulous patients: a retrospective study.

PURPOSE: The primary purposes of this study were: (1) to describe the number and types of complications patients had before and after insertion of a removable prosthesis (i.e., denture) following radiation therapy to the head and neck and (2) to investigate whether the time between radiation therapy and denture insertion might contribute to those complications. MATERIALS AND METHODS: This research evaluated edentulous patients and those who were rendered edentulous as a result of their cancer treatment. After obtaining institutional approval following HIPAA regulations, a total of 349 charts were identified: 152 patients from Houston Veterans Administration Medical Center (HVAMC) and 197 patients from M. D. Anderson Cancer Center (MDACC). A total of 190 patients met the inclusion criteria with data available for review. RESULTS: No significant differences were found in any of the comparisons made, except when comparing complications that occurred after the dentures were inserted and the amount of time it took for prosthetic rehabilitation. The majority of patients had no complications. The patients who received their dentures in 180 days or less had the same number of complications when compared with those patients who received their dentures in 181 to 365 days and those who had to wait longer than a year for prosthetic rehabilitation. Patients with more pre-insertion complications tended to have delayed prosthetic rehabilitation. Those patients who had complications both before and after denture insertion tended to have bilateral dosing of their radiation treatment. Patients who had received radiation therapy were 1.7 times more likely to have post-prosthesis insertion complications. The majority of patients who experienced complications before and after denture insertion had greater than 5000 cGy. CONCLUSIONS: The numbers of complications reviewed in this retrospective analysis were considerably fewer than the number expected. There appears to be no difference in the number of pre- and post-insertion complications as a function of the time delay from oral surgical procedure to start of radiation treatment (10 to 21 days vs. 22 days or more).

Adult↗

Treatment strategy for patients with ectodermal dysplasia: a case report.

Ectodermal dysplasia (ED) is a hereditary condition characterized by abnormal development of the skin, hair, nails, sweat glands, and the stomatognathic system. There are many different types of ectodermal dysplasia of which X-linked anhidrotic ectodermal dysplasia is the most common. Multiple genes have been discovered to cause ectodermal dysplasias. With any form of ED, children may display a range of symptoms and challenging rehabilitation. This clinical report presents the treatment plan for a young patient with ED and anodontia requiring prosthetic restoration.

Age Factors↗

Postsurgical use of prosthetic palatal appliances. Two case reports.

Patients with cleft lip or palate encounter a myriad of difficulties in their early years of life, some of which begin at birth. The defect often impairs suckling and deglutition in the neonate. It can hinder appropriate speech development and may impose undue social and psychological stresses. Surgical and orthodontic interventions are essential and prosthetic palatal appliances play an important role not only throughout the patient's treatment course, but also in the treatment of unfavorable surgical sequelae.

Child, Preschool↗

An orally bioavailable, functionally selective inverse agonist at the benzodiazepine site of GABAA alpha5 receptors with cognition enhancing properties.

(3-tert-Butyl-7-(5-methylisoxazol-3-yl)-2-(1-methyl-1H-1,2,4-triazol-5-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine (13) has been identified as a functionally selective, inverse agonist at the benzodiazepine site of GABA(A) alpha5 receptors. 13 is orally bioavailable, readily penetrates the CNS, and enhances performance in animal models of cognition. It does not exhibit the convulsant, proconvulsant, or anxiogenic activity associated with nonselective GABA(A) inverse agonists.

Administration, Oral↗