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Biomedical subjects

Mark S Chambers

Publications and source records attributed to Mark S Chambers.

36 records · Page 2Linked to original sources
PubMed2004

3,4-Dihydronaphthalen-1(2H)-ones: novel ligands for the benzodiazepine site of alpha5-containing GABAA receptors.

A series of substituted 3,4-dihydronaphthalen-1(2H)-ones with high binding affinity for the benzodiazepine site of GABAA receptors containing the alpha5-subunit has been identified. These compounds have consistently higher binding affinity for the GABAA alpha5 receptor subtype over the other benzodiazepine-sensitive GABAA receptor subtypes (alpha1, alpha2 and alpha3). Compounds with a range of efficacies for the benzodiazepine site of alpha5-containing GABAA receptors were identified, including the alpha5 inverse agonist 3,3-dimethyl-8-methylthio-5-(pyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 22 and the alpha5 agonist 8-ethylthio-3-methyl-5-(1-oxidopyridin-2-yl)-3,4-dihydronaphthalen-1(2H)-one 19.

Allosteric Site↗
PubMed2004

Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management.

BACKGROUND: Xerostomia is a common, debilitating complication of radiation therapy (RT) for head and neck cancer. This article reviews the pathogenesis of radiation-induced xerostomia, its impact on quality of life (QOL), and treatment options. METHODS: Virtually all patients undergoing RT for head and neck cancers have xerostomia, which causes oral discomfort and pain, increased dental caries and oral infection, and difficulty speaking and swallowing. This significantly impairs QOL and can compromise nutritional intake and continuity of cancer therapy. The literature describing pathogenesis, impact on QOL of radiation-induced xerostomia, and preventive and interventional therapies was reviewed. RESULTS: Current management strategies include stringent dental and oral hygiene; parotid-sparing radiation techniques to prevent or minimize xerostomia; and pharmacotherapies, such as salivary substitutes and sialogogues. Future strategies may include advanced three-dimensional intensity-modulated RT techniques, salivary gland transfer, newer sialogogues, and gene therapy. CONCLUSIONS: New treatment approaches to xerostomia from RT for head and neck cancer may result in significant improvement in patient QOL.

Head and Neck Neoplasms↗
PubMed2004

Risk of osteoradionecrosis after extraction of impacted third molars in irradiated head and neck cancer patients.

PURPOSE: This study was performed to compare the risk of osteoradionecrosis (ORN) in head and neck cancer patients in whom 1 or more impacted third molars were extracted before radiotherapy with patients whose impacted third molars were left intact. PATIENTS AND METHODS: Eighty-one patients were selected from the medical records from 1989 to 1998. Patients had at least 1 impacted third molar and received radiotherapy for a head and neck cancer. These patients were divided into 2 groups on the basis of preirradiation extraction: group 1, patients who had impacted third molars extracted before radiotherapy (n = 55), and group 2, patients whose impacted third molars were left intact before radiotherapy (n = 38). In 12 patients of combined groups 1 and 2, at least 1 but not all of the impacted third molars were extracted before radiotherapy. RESULTS: Before radiotherapy, a total of 99 impacted third molars were extracted from the 55 patients in group 1 and a total of 55 impacted third molars were left intact in the 38 patients in group 2. After radiotherapy, a total of 7 impacted third molars were removed from 5 patients as treatment for infection (5 lower molars) or discomfort (2 upper molars). A total of 4 patients (2 from group 1 and 2 from group 2) developed ORN in the mandible. Of these 4 cases of ORN, 1 from group 1 appeared to be related to a dry socket that developed after preirradiation extraction of a lower impacted third molar, 1 from group 2 seemed to be related to infection of a lower impacted third molar after radiotherapy, and the remaining 2 cases appeared to be unrelated to an impacted third molar. CONCLUSION: Because few patients in this study developed ORN, the study failed to demonstrate whether preirradiation extraction versus retention of impacted third molars affects the risk for ORN.

Adolescent↗
PubMed2004

Obturation of the partial soft palate defect.

A partially resected soft palate represents a more significant challenge for effective prosthodontic obturation than for complete soft palate resections. In fact, for some patients it may not be possible to prosthetically rehabilitate with partial soft palate resections, resulting in velopharyngeal dysfunction, which could include hypernasal voice quality and nasal regurgitation of food and liquids. This article presents a technique for recording the contours of a partial soft-palate defect for prosthetic obturation.

Denture Bases↗
PubMed2004

In vitro effect of microwave irradiation on the retentive force of magnets.

STATEMENT OF PROBLEM: Few studies have addressed the possible effect(s) of microwave irradiation on the magnetic properties of "permanent" magnets during the fabrication of dental and maxillofacial prostheses. PURPOSE: The objective of this study was to investigate the influence of microwave irradiation energy on the retentive force of a magnetic attachment system used in maxillofacial prosthetic rehabilitation. MATERIAL AND METHODS: A heat-polymerized PMMA disk (6 cm in diameter) was fabricated. Seven magnets were placed around the wafer in a circumferential fashion: 1 in the center and 6 surrounding it. The 7 magnets were spaced 2 cm from their respective centers. Seven heat-polymerized PMMA cylinders were also used, and a magnet (counter-magnet) was placed in the center of each even with the cylinder's surface. Once the investment had set (45 minutes after mixing), the 7 counter-magnets in the cylinders were placed against the 7 magnets in the acrylic wafer. A second mixture of investment material was added. The flasks were separated, and the acrylic wafer was removed to accommodate the 7 counter-magnets in the base mold in the same geometric configuration and to serve as a "spacer" for the silicone material. A 1:1 mixture of medical grade elastomer (MDX4-4210) and medical adhesive silicone (type A) was packed and compressed, the molds were reclamped, and the excess silicone was removed. The elastomer/silicone wafer was packed and compressed into the test and base molds, the molds were reclamped, and excess silicone was removed. The first group of magnets, designated Group A, received microwave irradiation for 5 minutes at low power (112 W). This procedure was repeated for each group of magnets at the following polymerizing times (n=14): Group B, 10 minutes; Group C, 15 minutes; Group D, 20 minutes; Group E, 25 minutes; Group F, 30 minutes; and Group G, 35 minutes. Measurements of retentive force (N) at 10 mm/min ramp rate of speed of separation was conducted. The specimen rate read 5.0 points/second. Data were analyzed using a 1-way analysis of variance (alpha=.05); individual mean values were compared using the Tukey test (alpha=.05). RESULTS: There were no statistical differences in retentive force between groups D, E, and F (20, 25, and 30 minutes, respectively) or between groups A, B, C, D, F, and G (5, 10, 15, 20, 30, and 35 minutes, respectively). When the microwave-irradiated groups A through G were compared with the control group, there was a significant difference (P<.05) in retentive force (N). Group E (25 minutes) showed the largest reduction of retentive force (0.3 N, a reduction of 12%). CONCLUSION: If a prosthesis is processed using a microwave and contains samarium cobalt magnets, the retentive force may be reduced up to 12% under specific conditions.

Cobalt↗
PubMed2004

A phase II study to assess the efficacy of amifostine for submandibular/sublingual salivary sparing during the treatment of head and neck cancer with intensity modulated radiation therapy for parotid salivary sparing.

Intensity modulated radiation therapy (IMRT) allows for relative parotid salivary gland sparing for patients undergoing treatment for head and neck squamous cell cancer, but is less reliable for sparing the submandibular glands. Cytoprotection with amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD) has been shown to decrease rates of acute and late xerostomia in patients undergoing radiation therapy for head and neck squamous cell cancer. The addition of amifostine to IMRT may augment parotid salivary sparing, and add submandibular/sublingual, and minor salivary gland sparing resulting in greater salivary flow rates and a more physiologic saliva. Eligible patients include those slated to receive definitive IMRT for early oropharynx cancer or postoperative RT, both without chemotherapy, for more advanced cancers. These include T1, T2 and favorable T3 (favorable, exophytic), N0-2b (small volume) M0 oropharynx cancers who are to receive bilateral neck RT. Postoperative patients with nodal metastases, T3 and T4 primaries, perineural invasion, and lymphovascular invasion will be eligible. Patients will receive 30 to 33 fractions. Clinical target volume (CTV) 1 will receive 60 to 66 Gy, CTV2 will receive 60 Gy, and CTV3 will receive 54 to 57 Gy. The mean dose goal for the parotid gland is 25 Gy. Patients will receive fixed-dose amifostine 500 mg subcutaneously 30 to 60 minutes before each radiation fraction. Subjective xerostomia questionnaires will be administered. Whole mouth and individual major salivary gland stimulated and unstimulated saliva will be collected before and after therapy at 6 weeks, 6 and 12 months. Xerostomia outcomes will be correlated with salivary dose volume histogram data. Accrual has not yet begun. The results of this study will give an indication of the objective and subjective benefit of combined IMRT physical parotid salivary sparing and amifostine chemical cytoprotection for combined salivary gland sparing and reduction in the rate of xerostomia in patients undergoing IMRT for head and neck squamous cell cancer.

Amifostine↗
PubMed2004

Sjögren's syndrome.

Saliva is an essential body fluid. It is important in maintaining oral health, taste acuity, mastication, deglutition and digestion, oral flora regulation, oral cleansing, voice acuity, and speech articulation. Saliva is composed largely of water but also contains minerals, electrolytes, buffers, enzymes, growth factors, cytokines, immunoglobulins, proteins, and metabolic waste products, with the concentrations and compositions of these components varying by individual. Many systemic disorders can affect salivary function, greatly compromising oral health. One such disorder is Sjögren's Syndrome (SS), an autoimmune exocrinopathy characterized by oral and ocular dryness with or without impairment of other organ systems. SS can cause substantial serologic autoimmune reactivity and in some instances is associated with other connective-tissue autoimmune disorders, such as rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. SS increases the risk for developing malignant non-Hodgkin's lymphoma. Treatment of this syndrome consists of a combination of multiple agents, depending on the degree of symptomatology: cholinergic agonists, artificial salivary substitutes, nonsteroidal anti-inflammatory agents, antirheumatic drugs, and biologic agents. This article describes saliva and salivary function, the pathogenesis of SS, the current treatment of xerostomia, and quality of life issues related to salivary dysfunction.

Cholinergic Agonists↗
PubMed2003

Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition.

In pursuit of a GABA(A) alpha5-subtype-selective inverse agonist to enhance cognition, a series of 6,7-dihydro-2-benzothiophen-4(5H)-ones has been identified as a novel class of GABA(A) receptor ligands. These thiophenes have higher binding affinity for the GABA(A) alpha5 receptor subtype compared to the GABA(A) alpha1, alpha2, and alpha3 subtypes, and several analogues exhibit high GABA(A) alpha5 receptor inverse agonism. 6,6-Dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one (43) has been identified as a full inverse agonist at the GABA(A) alpha5 receptor and is functionally selective over the other major GABA(A) receptor subtypes. 43 readily penetrates into the CNS to give selective occupancy of GABA(A) alpha5 receptors. In addition, 43 enhances cognitive performance in rats in the delayed 'matching-to-place' Morris water maze test-a hippocampal-dependent memory task-without the convulsant or proconvulsant activity associated with nonselective, GABA(A) receptor inverse agonists.

Animals↗
PubMed2003

A mold-making procedure for multiple orbital prostheses fabrication.

Traditional methods of fabricating orbital prostheses rely on the "lost wax" technique to produce a realistic representation of the sculpted pattern produced in the defect. The usual constituents of the mold that reproduces the subtleties of the palpebral fissure are often minute, making them prone to fracture and subsequent dissolution by repeated attempts at pressing each prosthesis. The following method provides a mold resistant to these problems with light-polymerized resin surrounding the palpebral part of the orbital mold.

Acrylic Resins↗
PubMed2003

Facial moulage: the effect of a retarder on compressive strength and working and setting times of irreversible hydrocolloid impression material.

STATEMENT OF PROBLEM: Irreversible hydrocolloid is widely used as an impression material for fabrication of extraoral maxillofacial impressions. A disadvantage of irreversible hydrocolloid, however, is its limited working time. PURPOSE: This study tested the compression strength (elastic recovery) and working and setting times for an irreversible hydrocolloid impression material after a retarder was added. MATERIAL AND METHODS: The irreversible hydrocolloid (Jeltrate) was mixed with water in a standard water/powder mixture of 18 mL (1 unit) of water and 7 g (1 unit) of the impression material. Test specimens (n = 3) were prepared by adding 2, 4, 6, and 8 drops of monobasic sodium phosphate (the retarder) to each. Three other specimens, to which no retarder was added, served as the control. Specimens were prepared according to the American National Standards Institute/American Dental Association's specification no.18 guidelines for irreversible hydrocolloid impression material. Immediately after the specimens were prepared, the flat end of a polished rod of poly(methyl methacrylate) was placed in contact with its exposed surface and quickly withdrawn. The working-time experiment was a pass/fail test conducted 30 seconds before the initial setting time. The initial setting time was established as extending from the start of the mix to the time when the impression material no longer adhered to the end of the rod. To determine how the compressive strength of the modified irreversible hydrocolloid (with retarder added) compared with that of the control, the mean stress at maximum load (Mpa) was analyzed. The compressive strength (MPa) was calculated. Statistical analysis consisted of descriptive statistics and regression analyses. RESULTS: The results of this experiment demonstrated that the elastic recovery of the irreversible hydrocolloid did not change with the addition of sodium phosphate (2 to 8 drops). The percent recovery with was 95.95% +/-.42%, 96.33% +/-.82%, and 96.28% +/-.53% for 0 (control), 2 and 8 drops, respectively. Average setting times for control specimens were 2 minutes 20 seconds +/- 0 seconds for the control specimen (0 drops) to 11 minutes 20 seconds +/- 1 minute 50 seconds for the test specimen with 8 drops. There was a direct relationship (R(2) = 0.85) between the number of drops added and the setting time. All control specimens and test specimens containing 2, 4, 6, and 8 drops of monobasic sodium phosphate produced acceptable levels of elastic recovery (> or =95%). CONCLUSION: Within the limitations of this study, predictable longer working and setting times were demonstrated for the irreversible hydrocolloid specimens with 1 to 8 drops of the sodium phosphate solution tested. The specimens with 8 drops of retarder solution exhibited variable setting times and would not be suitable for clinical use. The compressive strength of the modified irreversible hydrocolloid material tested was compromised because of the addition of sodium phosphate solution; however, recovery from deformation remained satisfactory as retarder solution was added.

Alginates↗
PubMed2003

Custom modification of the Blom-Singer tracheostoma valve housing.

A technique is presented for modifying the Blom-Singer tracheostoma valve housing to improve peristomal skin adherence for hands-free tracheoesophageal speech production following total laryngectomy. The finished product is thin, flexible, and maintains enhanced tear strength. The edges of a standard housing device for the Blom-Singer valve are trimmed to allow for better accommodation to the tissue surface without distortion. A punch biopsy instrument is used to cut uniform holes around the housing device to allow for permeation of the silicone mixture for better mechanical adherence of the materials.

Adhesives↗
PubMed2003

How I do it: a technique for oral wound irrigation following maxillectomy and mandibulectomy.

BACKGROUND: Numerous devices have been recommended for ensuring appropriate hygiene and care of wounds resulting from maxillectomy and mandibulectomy. This article describes an irrigation device for use in the oral cavity after these procedures. METHODS: The system consists of: a prepackaged, disposable, 50-cc piston syringe; a nonconductive connecting tube; and, a saliva ejector that can be assembled for oral irrigation. RESULTS: The modified piston syringe allows physicians, nurses, and patients to efficiently irrigate mucosal wounds, maxillary or mandibular defects, and oropharyngeal or oral and pharyngeal wounds. CONCLUSION: This system is efficacious, more adaptable, and less expensive than other self-irrigating gravimetic instruments and is thus recommended for use in patients who have undergone maxillectomy or other ablative procedures in the oral cavity.

Humans↗
PubMed2002

6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists.

Nonselective inverse agonists at the benzodiazepine binding site on the GABA-A chloride ion channel enhance cognitive performance in animals but cannot be used in the treatment of cognitive disorders because of anxiogenic and convulsant side effects. We have identified a novel series of GABA-A alpha5 receptor ligands during our search for alpha5 receptor inverse agonists as potential cognition enhancers. In particular, 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one (26) has been identified as a functionally selective GABA-A alpha5 inverse agonist.

Animals↗
PubMed2002

Modification of the Barton button for tracheoesophageal speech: an innovative maxillofacial prosthetic technique.

Laryngectomized, tracheoesophageal speakers who achieve hands-free speech wear a special breathing valve to automatically shunt air into the pharyngoesophagus for speech production. The standard method of attachment is adherence to the peristomal skin with glues and adhesives. The Barton button is a simpler, more efficient alternative that provides intraluminal attachment within the trachea. Although the device is appealing, constraints in standard design and dimensions have limited its success. This article presents a technique for modification of the Barton button to increase its successful use by tracheoesophageal speakers.

Equipment Design↗
PubMed2002

Anterior key method for indexing orbital prostheses.

This article describes a predictable method for indexing the ocular portion of an orbital prosthesis. Because indexing is performed from the anterior aspect of the cast, damage is minimized, fewer modifications are required, and the mold can be preserved for repeated use.

Acrylic Resins↗