Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system.

PURPOSE: Mucositis occurs in almost all patients treated with radiotherapy for head and neck cancer. The aim of this multicenter, double-blind, prospective, randomized trial was to evaluate the clinical efficacy of an economically viable antimicrobial lozenge (bacitracin, clotrimazole, and gentamicin [BcoG]) in the alleviation of radiation-induced mucositis in patients with head and neck cancer. PATIENTS AND METHODS: One hundred thirty-seven eligible patients were randomized to treatment with either antimicrobial lozenge (69 patients) or placebo lozenge (68 patients). The primary end point of the study was the time to development of severe mucositis from the start of radiotherapy. Secondary end points included severity and duration of mucositis, pain measurement, radiation therapy interruption, and quality of life. Mucositis was scored using a validated mucositis scoring system. RESULTS: Toxicity profiles were similar between the two arms of the study. The median time to development of severe mucositis from the start of radiotherapy was 3.61 weeks on BCoG and 3.96 weeks on placebo (P =.61). There were no statistically significant differences between the arms in the extent of severe mucositis as measured by physician, in oral toxicities as recorded by patients, or in radiotherapy delays. CONCLUSION: This study was conducted on the basis of a pilot study that demonstrated the BCoG lozenge to be tolerable and microbiologically efficacious. A validated mucositis scoring system was used. However, in this group of patients treated with conventional radiotherapy, the lozenge did not impact significantly on the severity of mucositis. Whether such a lozenge would be beneficial in treatment situations where rate of severe mucositis is higher (ie, in patients treated with unconventional fractionation or with concomitant chemotherapy) is unknown.

Selective COX-2 inhibitors: a review of their therapeutic potential and safety in dentistry.

Anti-inflammatory analgesics are commonly used medications in dental and medical practice. Their uses in dentistry include use as analgesics and as anti-inflammatory agents. In addition, antipyretic action accompanies the medication. The action of these groups of drugs depends on the dose provided. Analgesic and antipyretic effects occur at low dose, whereas analgesic effects occur at high dose. Among the common side effects of this class of medications are gastrointestinal irritation with potential for ulceration, increased tendency for bleeding due to antiplatelet effects, and long-term chronic dosing effects on renal function may occur. Recent developments in the anti-inflammatory group of medications include the introduction of cyclooxygenase-II inhibitors. These agents offer potentially significant advantages because of their relative lack of gastrointestinal irritation. Because of this, it is likely that these medications will be frequently used in the management of dental and medical conditions. Patients will present while on these medications, and these agents may serve as medications for management of dental pain, postsurgical pain, and for anti-inflammatory effects. The current literature indicates that COX-2 inhibitors offer substantial benefits because of their favorable gastrointestinal profiles and because of their lack of effect on platelet function.

Understanding "alternative" dental products.

Alternative, complementary, integrative, and holistic health care are matters of public interest and include oral and dental care products. There are a variety of dental products promoted as "alternatives" to the standard commercial dental products that most dentists recommend and most patients use. These alternative products can be categorized as standard dental products made with natural ingredients, herbal products, homeopathic products, and synthetic alternative products. Dental health care providers should be aware of the range of "alternative" dental products and be able to counsel their patients to understand the type of support and evidence needed to determine safety and efficacy of treatment. The use of dental care products should be based upon sound basic science and sufficient clinical evidence of safety and efficacy.

Perception of facial esthetics by native Chinese participants by using manipulated digital imagery techniques.

This investigation utilized a manipulated digital video imaging model to elicit profile facial esthetics preferences in a lay population of native Chinese participants from Beijing. A series of 4 distinct digitized distortions were constructed from an initial lateral cephalogram. These images represented skeletal or dental changes that differed by 2 standard deviations from the normative values for Chinese adults. Video morphing then created soft-tissue profiles. A series of nonparametric tests validated the digitized distortion model. The native Chinese participants in this sample found that the profile distortions most acceptable were the "flatter", or bimaxillary retrusive distortion, in the male stimulus face and the "anterior divergent", or maxillary deficiency, in the female stimulus face.

Effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia.

PURPOSE: We tested the effects of a saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia (BPH) via a randomized, placebo controlled trial. MATERIALS AND METHODS: We randomized 44 men 45 to 80 years old with symptomatic BPH into a trial of a saw palmetto herbal blend versus placebo. End points included routine clinical measures (symptom score, uroflowmetry and post-void residual urine volume), blood chemistry studies (prostate specific antigen, sex hormones and multiphasic analysis), prostate volumetrics by magnetic resonance imaging, and prostate biopsy for zonal tissue morphometry and semiquantitative histology studies. RESULTS: Saw palmetto herbal blend and placebo groups had improved clinical parameters with a slight advantage in the saw palmetto group (not statistically significant). Neither prostate specific antigen nor prostate volume changed from baseline. Prostate epithelial contraction was noted, especially in the transition zone, where percent epithelium decreased from 17.8% at baseline to 10.7% after 6 months of saw palmetto herbal blend (p <0.01). Histological studies showed that the percent of atrophic glands increased from 25. 2% to 40.9% after treatment with saw palmetto herbal blend (p <0.01). The mechanism of action appeared to be nonhormonal but it was not identified by tissue studies of apoptosis, cellular proliferation, angiogenesis, growth factors or androgen receptor expression. We noted no adverse effects of saw palmetto herbal blend. When the study was no longer blinded, 41 men elected to continue therapy in an open label extension. CONCLUSIONS: Saw palmetto herbal blend appears to be a safe, highly desirable option for men with moderately symptomatic BPH. The secondary outcome measures of clinical effect in our study were only slightly better for saw palmetto herbal blend than placebo (not statistically significant). However, saw palmetto herbal blend therapy was associated with epithelial contraction, especially in the transition zone (p <0.01), indicating a possible mechanism of action underlying the clinical significance detected in other studies.

Neural network prediction of prostate tissue composition based on magnetic resonance imaging analysis. A pilot study.

OBJECTIVE: To develop a neural network model that estimates prostate histology using magnetic resonance imaging (MRI). STUDY DESIGN: Fifty-three men with lower urinary tract symptoms (average age = 63.8 +/- 8.9 years) underwent a prostate MRI (T2) and sextant biopsy of the prostate. Masson Trichome and immunohistochemical prostate-specific antigen staining of the biopsy material were used to calculate the amount of stroma and epithelium in the inner gland (central plus transition zone). MRIs were normalized to the mean intensity of the obturator internus muscle for comparative analyses. Gray scale and texture features were extracted from the inner gland in the midsection transverse MRI slice. Clinical and image variables were used in two neural networks predicting a high amount of stroma and a high amount of epithelium, respectively. RESULTS: The positive and negative predictive values of the stroma and epithelium neural networks were 95%, 69% and 65%, 92%, respectively. CONCLUSION: These data suggest that the combined use of these neural networks may predict patient response to medical therapy targeting prostatic stroma or epithelium.

Unconventional dentistry: Part IV. Unconventional dental practices and products.

This is the fourth in a series of 5 articles providing a contemporary overview and introduction to unconventional dentistry (UD) and its correlation to unconventional medicine (UM). Several common UD and UM practices are described to familiarize practitioners with a variety of theories, practices, products and treatments that specifically apply to dentistry. This brief review is not intended as an in-depth resource.

Marijuana initiates and their impact on future drug abuse treatment need.

This paper presents estimates of the number of people who will need treatment for illicit drug abuse problems for the years 2000 through 2020. The methodology employs logistic regression models, with treatment need as a dependent variable, using data from lifetime marijuana users included in the National Household Survey on Drug Abuse. Age at first use of marijuana was found to be the most important predictor in these models. Other variables included in the models were age, gender, and race/ethnicity. By generating estimates under alternative assumptions about future rates of initiation, it was projected that if current rates of initiation continue, treatment need will increase by 57% by 2020, and that the need for treatment will remain high even if initiation rates decrease dramatically, because of the aging baby boom cohort.

Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils.

BACKGROUND: As assessed by flow cytometry, the increase in hydrogen peroxide in individual neutrophils from old volunteers was significantly greater than in neutrophils from young volunteers. To explain the discrepancy in previous reports that showed reduced superoxide generation with age and our finding, we measured the kinetics of antioxidative enzymes. METHODS: Neutrophils were obtained from young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen peroxide following stimulation with formyl peptide in individual neutrophils was assessed by flow cytometry by using dihydrorhodamine 123. The enzyme kinetics was determined from the best fit curve using Michaelis-Menten equations. RESULTS: Aging was associated with a significant reduction in the Vmax for glutathione peroxidase. The decreased activity was not due to selenium deficiency as the serum and neutrophil concentrations were identical with age. Following activation, a significant increase in the Km was noted in neutrophils from young but not from old volunteers. CONCLUSIONS: These results account for the increased intracellular accumulation of hydrogen peroxide as a function of age in stimulated neutrophils. These results provide evidence in humans of an age-related impairment in antioxidative defense mechanisms that support the free radical theory of aging.

Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function.

Ultraviolet light (UVR) induces a myriad of cutaneous changes, including delayed disruption of the permeability barrier with higher doses. To investigate the basis for the UVB-induced barrier alteration, we assessed the epidermal lamellar body secretory system at various time points before and after barrier disruption with a single high dose of UVB (7.5 MED) to murine epidermis. Morphological data were correlated with changes in epidermal proliferation and lipid synthesis, indicative of lamellar body generation. Twenty-four hours following UVB, the stratum corneum (SC) is normal, but a layer of abnormal, vacuolated, and lamellar body (LB)-deficient cells is present, immediately beneath the stratum granulosum (SG)/SC interface. Immediately subjacent to this band of damaged cells, normal keratinocytes that contain intact LBs are present. By 72 h, concomitant with the appearance of a barrier abnormality, extensively damaged cells persist at the SC/SG interface, and abnormal lamellar membrane structures appear in the lower SC. Upper stratum spinosum (SS) and lower SG cells appear normal, with increased numbers of LBs. A barrier abnormality is still present at 96 h, in association with membrane abnormalities in the lower SC interstices, but up to four normal appearing, subjacent SG cell layers are present. By 120 h, accelerated LB formation and precocious LB extrusion occur throughout the thickened SG; normal lamellar membranes are present in the lower SC; and barrier recovery is almost complete. Whereas, epidermal synthesis of the major barrier lipid species (i.e., cholesterol, fatty acids, and ceramides, including acylceramides) is reduced or unchanged at 24 and 48 h, it increases significantly 72 h after exposure to UVB. Therefore, the delayed disruption of the permeability barrier following acute UVB exposure results from the arrival of a band of lamellar body-incompetent (i.e., damaged) cells at the SG/SC interface. The subsequent, rapid recovery of the barrier, in turn, results from compensatory hyperplasia of subjacent, undamaged SS/SG cells, generating increased numbers and contents of LB. These results underscore the critical role of the stratum compactum in mediating barrier function, and suggest that beneficial therapeutic effects of UV exposure may be due to enhanced lipid production and barrier regeneration.

Postradiation osteonecrosis of the mandible: a long-term follow-up study.

OBJECTIVES: The objective of this study was to assess the long-term progress of 26 patients who experienced postradiation osteonecrosis of the jaw between 1975 and 1989. STUDY DESIGN: Of 26 patients who had been previously managed with hyperbaric oxygen therapy as a part of their treatment for postradiation osteonecrosis of the jaw, 20 were evaluated to determine their current status of the condition: resolved, chronic persisting (unresolved), or active progressive (symptomatic). RESULTS: Two of 20 patients experienced recurrences of the condition. In one of these patients, surgical treatment was identified as the stimulus of postradiation osteonecrosis. In the other patient, the recurrence appeared to be related to periodontal disease activity. In 60% (12 of 20) of the patients, the condition remained resolved, improvement in clinical staging occurred in 10% (2 of 20) (from symptomatic to unresolved or resolved), and 20% (5 of 20) of the patients continued to demonstrate chronic persisting postradiation osteonecrosis at the end of the long-term follow-up period. CONCLUSION: This study supports the contention that postradiation osteonecrosis can occur at any time after radiation therapy, and that patients remain at risk up to 231 months after treatment of the cancer and probably indefinitely after radiation therapy. Our findings also suggest that risk of second episodes of the condition after management of an initial episode is low. In addition, our follow-up study revealed that chronic nonprogressive postradiation osteonecrosis can remain stable without extensive intervention including combined hyperbaric oxygen therapy and surgery.

A comparison of TMD patients with or without prior motor vehicle accident involvement: treatment and outcomes.

The influence of previous trauma in the management of patients with temporomandibular disorders (TMD) is controversial. The objectives of this study were to compare treatment regimens and outcomes in motor vehicle accident trauma-related versus nontrauma-related TMD patients. Files of 50 trauma and 50 matched nontrauma TMD patients were reviewed. Information concerning treatment received, progress of symptoms with treatment, and findings from the final examination were recorded. As a whole group, posttraumatic TMD patients tended to receive more types of treatment (P < .0001), have more medications prescribed (including analgesics, P < .001; nonsteroidal anti-inflammatory drugs, P = .001; muscle relaxants, P = .001; and tricyclic antidepressants, P < .001), have more oral medicine clinic visits (P = .07) over a longer period of time (P = .06), and have a poorer treatment outcome (P < .001) as compared to the nontrauma group. When the patients were separated into TMD diagnostic classification subsets, only some of these differences between trauma and nontrauma patients were seen, but the subset group sizes were small and only a few of the groups could be compared. There did not seem to be a significant effect from settling insurance claims prior to the last clinic visit. Trauma may be an important prognostic factor in the management of some TMD patients.

Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism.

OBJECTIVE: Chemotherapy doses are limited by toxicity to normal tissues. Intravenous glutamine protects liver cells from oxidant injury by increasing intracellular glutathione (GSH) content. The authors hypothesized that supplemental oral glutamine (GLN) would increase the therapeutic index of methotrexate (MTX) by improving host tolerance through changes in glutathione metabolism. The authors examined the effects of oral glutamine on tumor and host glutathione metabolism and response to methotrexate. METHODS: Thirty-six 300-g Fischer 344 rats were implanted with fibrosarcomas. On day 21 after implantation, rats were randomized to receive isonitrogenous isocaloric diets containing 1 g/kg/day glutamine or glycine (GLY) by gavage. On day 23 after 2 days of prefeeding, rats were randomized to one of the following four groups receiving an intraperitoneal injection of methotrexate (20 mg/kg) or saline (CON): GLN+MTX, GLY+MTX, GLN-CON, or GLY-CON. On day 24, rats were killed and studied for arterial glutamine concentration, tumor volume, kidney and gut glutaminase activity, and glutathione content (tumor, gut, heart, liver, muscle, kidney, and lung). RESULTS: Provision of the glutamine-enriched diets to rats receiving MTX decreased tumor glutathione (2.38 +/- 0.17 in GLN+MTX vs. 2.92 +/- 0.20 in GLY+MTX, p < 0.05), whereas increasing or maintaining host glutathione stores (in gut, 2.60 +/- 0.28 in GLN+MTX vs. 1.93 +/- 0.18; in GLY+MTX, p < 0.05). Depressed glutathione levels in tumor cells increases susceptibility to chemotherapy. Significantly decreased glutathione content in tumor cells in the GLN+MTX group correlated with enhanced tumor volume loss (-0.8 +/- 1.0 mL in GLN+MTX vs. +9.5 +/- 2.0 mL in GLY+MTX, p < 0.05). CONCLUSION: These data suggest that oral glutamine supplementation will enhance the selectivity of antitumor drugs by protecting normal tissues from and possibly sensitizing tumor cells to chemotherapy treatment-related injury.

Topical application of capsaicin for treatment of oral neuropathic pain and trigeminal neuralgia.

Neuropathic pain may be a major cause of pain in the head and neck. Trigeminal neuralgia may appear as intraoral pain. This article reviews a series of 24 consecutive cases of oral pain treated with topical capsaicin. Complete remission of neuropathic pain was seen in 31.6% of patients; partial remission was achieved in 31.6% of patients. Trigeminal neuralgia with an intraoral trigger was less responsive to topical therapy than neuropathic pain. Further study is needed to clarify the efficacy of topical capsaicin in neuropathic and neuralgic pain and the effect of differing dosages and frequency of application. On the basis of the findings in this open-label clinical trial, controlled clinical study of capsaicin in neuropathic oral pain states appears warranted.

Hyperbaric oxygen and postradiation osteonecrosis of the mandible.

The clinical and dental records of 26 patients with the clinical diagnosis of postradiation osteonecrosis (PRON) managed with hyperbaric oxygen (HBO) were reviewed to determine the efficacy of HBO. 19 patients were male and 7 were female; age at the first HBO session ranged from 28 to 80 years (median 57.5 years). All but 8 patients reviewed had some form of surgical management; 7 had mandibulectomy for PRON. As part of management, a total of 9-84 HBO sessions (median 35 sessions) was administered. 18 of the 26 patients ultimately achieved persistent mucosal and cutaneous coverage 1-84 months (median 24 months) after the first HBO session. 13 of the 26 patients met strict criteria for resolution of their disease; fully 21 of 26 patients had improved PRON status following HBO therapy. HBO treatment as part of a comprehensive management plan is safe and effective in the management of PRON.

Bone and gallium scans in postradiotherapy osteonecrosis of the jaw.

The role of radiographic and nuclear imaging in evaluation of postradiotherapy osteonecrosis of the jaw was studied. Patients who had received imaging at diagnosis and following hyperbaric oxygen therapy were studied. Radiographic changes did not correlate with the clinical status of patients. All bone scans were abnormal at the time of diagnosis of osteonecrosis, but remained abnormal following changes in the clinical status of patients. Thus, the bone scan may aid in the detection of osteonecrosis. Gallium uptake did not aid i diagnosis, but did correlate with clinical findings following treatment. Persisting positive gallium scans may indicate the need for surgery following hyperbaric oxygen therapy.

Photocarcinogenesis promotion studies with benzoyl peroxide (BPO) and croton oil.

Previous studies demonstrated that BPO can promote chemically initiated tumor formation in SENCAR mice. In addition, a number of chemicals have been shown to promote and/or enhance UVR induced carcinogenesis. This study examined the effect of BPO on UVR initiated tumor formation. One hundred and forty-eight Uscd mice received 270 mJ/cm2 of UVB radiation to the posterior halves of their backs 3 times a week for 8 weeks. Four weeks later the mice were divided into 4 groups. Group I received croton oil in acetone applications to the back 5 times a week for the duration of the study. Group II received acetone, Group III received the BPO diluent, and Group IV received the BPO in an aqueous diluent applications as in Group I. One mouse in Group II (acetone) and one in Group IV (BPO) developed tumors in unirradiated skin. In the UVR initiated skin 38% of the survivors developed tumors in Group I (croton oil), whereas 5% did in Group II (acetone), 8% in Group III (BPO base), and 8% group IV (BPO). Thus under the circumstances of this study croton oil did promote UV initiated tumor formation but BPO did not. These results are consistent with those recently reported by Iversen.