Associations between patient-reported late effects and systemic cytokines in long-term survivors of head and neck cancer treated with radiotherapy.

PURPOSE: Head and neck cancer (HNC) treatment may lead to late effects and impaired health-related quality of life of survivors. Knowledge on long-term late effects after radiotherapy (RT) and potential underlying biological mechanisms is lacking. We assessed the prevalence of xerostomia, dysphagia, and chronic fatigue (CF) in HNC survivors ≥ 5 years post-RT, and examined associations between pro-inflammatory cytokines and late effects. METHODS: In a cross-sectional study, 263 HNC survivors treated between 2007 and 2013 were enrolled. They completed validated questionnaires assessing xerostomia and dysphagia (the EORTC QLQ-H&N35), and CF (the Fatigue Questionnaire), and underwent blood sampling and clinical examination. Pro-inflammatory cytokines were analyzed in 262 survivors and 100 healthy age- and gender-matched controls. RESULTS: Median time since treatment was 8.5 years. The proportions of survivors reporting xerostomia, dysphagia, and CF were 58%, 31%, and 33%, respectively, with a preponderance of females. We found no significant associations between IL-6, IL-8, IP-10, TARC, TNF, or ENA-78 and the three late effects. The odds of having elevated levels of IL-6 and IP-10 were significantly higher in the survivors compared to the controls. CONCLUSIONS: More than one-third of long-term HNC survivors experienced xerostomia, dysphagia, and CF. Persistent inflammation, with elevated systemic cytokines, was not associated with these late effects, although HNC survivors had higher levels of some cytokines than the controls. IMPLICATIONS FOR CANCER SURVIVORS: This study provides new knowledge on late effects that can serve as grounds for informing patients with HNC about risk of late effects more than 5 years after RT.

Patients with non-Sjögren's sicca report poorer general and oral health-related quality of life than patients with Sjögren's syndrome: a cross-sectional study.

Understanding the impact of the disease on quality of life is crucial in patient management. In this cross-sectional study, general and oral health-related quality of life questionnaires, and thorough examinations of oral and ocular dryness were performed in age- and sex-matched patients with primary Sjögren's syndrome (pSS group), non-Sjögren's syndrome sicca (non-SS group) and healthy controls. General and oral health-related quality of life were investigated with the 36-Item Short Form Health Survey and the 14-Item Oral Health Impact Profile questionnaires, respectively. Subjective symptoms of xerostomia and ocular dryness were recorded using the Summated Xerostomia Inventory and Ocular Surface Disease Index, respectively. Clinical examinations included evaluation of clinical oral dryness scores, candida counts, unstimulated and stimulated saliva secretory rates, tear osmolarity, tear film break-up time, Schirmer I test and ocular surface staining. Both patient groups had pronounced signs and symptoms of xerostomia and ocular dryness. Even though the non-SS patients had less severe clinical signs than the pSS patients, they demonstrated much poorer general and oral health-related quality of life. In conclusion, non-SS patients require more attention in order to improve their quality of life.

Orofacial granulomatosis: a questionnaire study among Norwegian dental clinicians.

AIMS: To evaluate awareness on orofacial granulomatosis (OFG) and oral Crohn disease (oral CD) among Norwegian dental clinicians. METHODS: A precoded questionnaire (QuestBack) was sent electronically to dentists and dental hygienists treating children and adolescents in the public dental service (PDS) in Norway. Data on the clinicians' knowledge of OFG and oral CD related to working experience were analysed by Chi square tests and bivariate logistic regression analyses. RESULTS: A total of 1097 clinicians were invited to participate, 778 dentists and 319 dental hygienists; 48.2% returned the completed form. Fifty-four percent of the participants had ≥ 10 year experience of clinical practice. Two-thirds (68.4%) of the dentists and all but one of the dental hygienists graduated in Norway. Approximately half of the respondents were aware of OFG (41.2%) and oral CD (57.8%). One-quarter (24.6%) reported that they most likely had seen a patient with OFG and 20.6% with oral CD. Recently graduated dentists (≤ 10 years ago) were more aware of OFG and oral CD than those who graduated > 10 years ago (p ≤ 0.001). Regarding dental hygienists, this difference was observed for OFG only (p < 0.05). Country of education did not affect the clinicians' reported knowledge. Approximately 90% would refer a patient suspected of having OFG or oral CD either to a dental specialist or to a physician. CONCLUSION: The high prevalence of clinicians observing OFG and oral CD in this study may indicate that OFG and/or oral CD are under-reported and that OFG in particular is more common than hitherto believed. The high frequency of awareness was promising for the benefit of the patients.

Evidence to support the hypothesis of tuberculosis as a cause of extreme osteonecrosis and osteomyelitis of the mandible in a West African population.

Maxillofacial tuberculosis (TB) is rare. The cases of 19 patients showing extreme bony destruction in the mandible, collected over a 3-month period in West Africa, are presented. Clinical, radiographic, and histological evidence indicated Mycobacterium tuberculosis as a possible cause. Further studies are in progress.

Sixty cases of extreme osteonecrosis and osteomyelitis of the mandible and maxilla in a West African population.

A description of 60 cases of extreme osteonecrosis and osteomyelitis of the jaws is presented. The patients attended the dental clinics of the medical charity organisation Mercy Ships, over a 2.5-year period when the hospital ship the 'Africa Mercy' was docked in the West African countries of Liberia, Benin and Togo. Possible reasons for the development of these clinical conditions are discussed including aetiologies, genetics (coagulopathies, osteopetrosis), Gorham's disease, infective conditions (tuberculosis, herpes zoster, HIV infection, osteomyelitis), toxicity (bisphosphonates, spider bites), and environmental effects (phossy jaw, radium jaw). The possible causes of these cases of osteonecrosis and osteomyelitis of the jaw are under investigation.

Norwegian LongoVital and recurrent aphthous ulceration: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: LongoVital (LV) is a herbal-based tablet enriched with the recommended daily doses of vitamins. The present study was undertaken to investigate possible prevention of recurrent aphthous ulceration (RAU) during 4 months daily intake of the Norwegian LV. DESIGN: The study was a placebo-controlled, double-blind, randomized, clinical trial. SUBJECTS: Sixty otherwise healthy patients with at least one attack of minor RAU per 2 months were included in the study. METHODS: After an introduction period (IP) of 60 days, the patients were randomly divided into three groups and given either LV, the herbs of LV only, or placebo. Three test tablets were taken every day together with breakfast for 4 months [tablet period (TP)] and the patients followed up for another 4 months (F-UP). The number of new ulcers (NU) and ulcer-free days (UFD) were observed. RESULTS: Fifty-two patients completed the study. Neither NU nor UFD showed any statistical significant differences between any of the groups in any of the periods. All three groups, however, showed a significant increase in UFD during the first 2 months of TP compared to IP. Within the LV group only, there was a further increase in UFD after 2 months intake of the tablets. The number of NU and UFD decreased significantly in both the LV and the herbal group in F-UP compared with TP. CONCLUSION: Neither the Norwegian LV nor the herbal component alone was superior to placebo in the prevention of RAU. The results, however, indicate that neither the LV nor the herbal group benefited from the treatment.

Oral mucosal side effects of cytotoxic chemotherapy of testicular cancer. A retrospective study.

Cancer chemotherapy often leads to injury of normal cells. Adverse effects on oral mucosa have been documented for several cytotoxic treatment regimens. The aim of the present retrospective study was to evaluate incidence and degree of oral soft tissue side-effects of a cisplatin-based chemotherapy regimen used for treating testicular cancer. The study was based upon a questionnaire mailed to 56 consecutive patients treated at the Norwegian Radium Hospital. A total of 39 individuals joined the study, as 2 patients refused and 15 did not reply. The patients were divided into two groups, a case group (24 individuals) having received 4 7 cycles of cisplatin-based chemotherapy in addition to surgery, and a control group (15 individuals) treated with surgery alone. The study revealed that 62% of the patients in the chemotherapy group developed adverse soft tissue reactions, with mucositis and pain as chief complaints, whereas none in the control group experienced any mucosal complications.

Increased human gingival blood flow induced by sodium lauryl sulfate.

Laser Doppler flowmetry was used in 14 subjects to investigate the effect of sodium lauryl sulfate (SLS) on gingival microcirculation. SLS, the most widely used detergent in toothpastes, exhibits a denaturing property, increases oral mucosal permeability and may cause epithelial desquamation of oral soft tissues. Gingival blood flow (GBF) was measured bilaterally 3 mm above the gingival margin, between the central and lateral maxillary incisors, before and after application of 1.5% SLS for 90 s to the gingiva on one side. The contralateral side served as a control with water application only. Relative changes in GBF were measured for 15 min on both sides. SLS increased the median GBF significantly between the 2nd and 10th min with a peak at 8 min, whereafter the flow decreased towards baseline. On the contralateral side, GBF initially declined before returning to baseline. 10 subjects felt a burning pain from the gingiva after SLS application and GBF increased in all of them. SLS increased the relative gingival blood flow presumably due to its penetrating and irritative properties, which resulted in vasodilatation. Laser Doppler flowmetry may be a useful non-invasive method for intraoral testing of different agents meant for oral use.

The effects of sodium lauryl sulfate on the phrenic nerve diaphragm preparation from the rat.

The time period to 50% inhibition of the twitches and compound action potential of the rat phrenic nerve-diaphragm preparation with sodium lauryl sulfate (2.5 x 10(-4)-5.0 x 10(-3)M) was recorded. The twitch contractions during indirect stimulation, the contraction during direct stimulation, and the compound action potential of the isolated phrenic nerve, were inhibited in that order. Depolarization due to high action potential activity induced by tetanic stimulation, veratridine, low Ca(2+)-or high K(+)-solutions, all enhanced the inhibitory effect of sodium lauryl sulfate (5.0 x 10(-4)M) during indirect stimulation. Hyperpolarization in K(+)-free solution and membrane stabilization by lidocaine antagonized the inhibitory effect of sodium lauryl sulfate. Accordingly, it probably induced inhibition by depolarization. The depolarization may decrease the influx of Ca2+ and the reuptake of choline+, as suggested by an observed synergism with tetraethylammonium CI and hemicholinium-3 Br, which antagonize the reuptake of choline+. On the opposite, 3,4-diaminopyridine, which increases the influx of Ca2+, antagonized the sodium lauryl sulfate-induced inhibition, and induced a biphasic contracture. The first phase was probably caused by a depolarization, and the second phase by release of Ca2+ from the sarcoplasmic reticulum. The potentiation of the second phase by dantrolene and in low Ca2+ solution, was attributed to sodium lauryl sulfate-induced desensitization.

Mouthrinses containing triclosan reduce the incidence of recurrent aphthous ulcers (RAU).

Triclosan, an antibacterial agent introduced in toothpastes and mouthrinses, has recently been shown to have anti-inflammatory and analgesic properties. The aim of the present double-blind cross-over study was to examine the effect of triclosan on the incidence of recurrent aphthous ulceration (RAU) when administered in mouthrinses. The study included 30 patients with a history of multiple recurrent aphthous ulcers. Three different triclosan-containing mouthrinses, differing only in their solubilizing agents were used and compared with a control rinse. The number of new ulcers, ulcer-free days and the severity of pain were recorded. The results showed that the patients experienced a significant decrease in the number of oral ulcers during the experimental period when the mouthrinses contained triclosan. It may thus be concluded that triclosan has the potential to reduce the number of aphthous ulcers presumably due to its anti-inflammatory properties.

The effect of two toothpaste detergents on the frequency of recurrent aphthous ulcers.

The aim of the present clinical double-blind crossover study was to investigate the effect of two different toothpaste detergents, sodium lauryl sulfate (SLS) and cocoamidopropyl betaine (CAPB), as compared with a detergent-free paste, on 30 patients with frequent occurrences of recurrent aphthous ulcers. The study consisted of three 6-week periods during which the patients brushed twice daily with the different test toothpastes. The localization and number of new ulcers were assessed. A significantly higher frequency of aphthous ulcers was demonstrated when the patients brushed with an SLS- than with a CAPB-containing or a detergent-free placebo paste. An SLS-free toothpaste may thus be recommended for patients with recurrent aphthous ulcers.

Oral mucosal desquamation of pre- and post-menopausal women. A comparison of response to sodium lauryl sulphate in toothpastes.

The aim of the present study was to investigate whether a difference in susceptibility to chemically induced irritation of the oral mucosa in 14 pre- and 14 post-menopausal women exists, following local exposure to sodium lauryl sulphate (SLS) in toothpastes. 4 different pastes differing only in detergent concentration present, or not, were used. The participants applied 1 cm of the different test toothpastes to a cap splint covering the teeth and the oral mucosa of the upper jaw 2 x daily for 2 min during a period of 4 days. 42 desquamative reactions of the oral mucosa (in 20 subjects) were observed, 29 and 13 in the pre- and the post-menopausal group, respectively. Desquamation was only experienced following exposure to SLS-containing toothpastes, not succeeding SLS-free paste. The results demonstrated that oral mucosa of pre-menopausal women was significantly more sensitive to SLS than oral mucosa of post-menopausal women. The difference in mucosal irritation between the 2 groups increased with increasing concentration of SLS.

Oral mucosal desquamation caused by two toothpaste detergents in an experimental model.

Sodium lauryl sulfate (SLS), the most widely used detergent in toothpastes, has been reported to cause adverse effects on oral soft tissues. This double-blind cross-over study describes the oral mucosal effects of SLS-containing toothpastes and pastes containing a zwitterionic detergent, cocoamidopropyl-betaine (CAPB) in an experimental model in 28 healthy females. Seven toothpastes, differing only in detergent concentration and/or type, were used: SLS (0.5, 1.0, 1.5%), CAPB (0.64, 1.27, 1.90%) and a placebo. Each participant applied 1 cm of assigned test toothpaste via a cap splint to the teeth and the mucosa of the upper jaw. The splints were used twice daily for 2 min during a period of 4 d, after which the participants were examined for oral desquamation. No other oral hygiene was allowed during the test periods. Ten days brushing with a detergent-free toothpaste was performed between each test period. Forty-five desquamative reactions were observed in 21 of 27 subjects (one was excluded) during the trial. Forty-two reactions were recorded during the SLS periods and the remaining three during the CAPB periods. The detergent-free toothpaste did not result in oral desquamation. SLS in toothpastes significantly increased the incidence of desquamation of the oral mucosa compared with toothpastes containing the detergent CAPB. The model used is not directly relevant to normal toothbrushing with toothpaste, but indicates that sensitive patients may contract mucosal irritation through SLS in toothpastes. Less toxic detergents, e.g. CAPB, are desirable in oral hygiene products.

Inhibitory effects of HgCl2 on excitation-secretion coupling at the motor nerve terminal and excitation-contraction coupling in the muscle cell.

1. Indirect and direct twitch (0.1-Hz) stimulation of the rat phrenic nerve-diaphragm disclosed that the inhibitory effect of HgCl2, 3.7 x 10(-5) M, on the neuromuscular transmission and in the muscle cell, was accelerated by 10-sec periods of 50-Hz tetanic stimulation every 10 min. This activity-dependent enhancement suggested an inhibitory mechanism of HgCl2 related to the development of fatigue, like membrane depolarization or decreased excitability, decreased availability of transmitter, or interference with the factors controlling excitation-secretion coupling of the nerve terminal, i.e. (Ca2+)0 or (Ca2+)i, and excitation-contraction coupling in the muscle cell, i.e., (Ca2+)i. 2. During both indirect and direct stimulation, HgCl2-induced inhibition was enhanced markedly by pretreatment with caffeine, which releases Ca2+ from endoplasmic and sarcoplasmic reticulum in the nerve terminal and muscle cell, respectively. This caffeine-induced enhancement was completely antagonized by dantrolene, which inhibits the caffeine-induced release. However, dantrolene alone did not antagonize the HgCl2-induced inhibition. 3. Since caffeine depletes the intracellular Ca2+ stores of the smooth endoplasmic reticulum, HgCl2 probably inhibits by binding to SH groups of transport proteins conveying the messenger function of (Ca2+)i. In the muscle cell this leads to inhibition of contraction. In the nerve terminal, an additional enhancement of the HgCl2-induced inhibition, by inhibiting reuptake of choline by TEA and tetanic stimulation, suggested that HgCl2 inhibited a (Ca2+)i signal necessary for this limiting factor in resynthesis of acetylcholine. 4. The (Ca2+)0 signal necessary for stimulus-induced release of acetylcholine was not affected by HgCl2. Hyperpolarization in K(+)-free solution antagonized the inhibitory effect of HgCl2 at indirect stimulation, and Ca(2+)-free solution enhanced the inhibitory effect at direct stimulation. K+ depolarization, membrane electric field increase with high Ca2+, membrane stabilization with lidocaine, and half-threshold stimulation, did not change the inhibitory effect of HgCl CH3HgCl. 1.85 x 10(-5) M, disclosed a synergistic interaction with caffeine during direct, but not during indirect, stimulation.

Sodium lauryl sulfate and recurrent aphthous ulcers. A preliminary study.

Sodium lauryl sulfate (SLS), a synthetic detergent commonly used in dentifrices, is an effective denaturant. The aim of the present study was to investigate the effect of SLS in patients with recurrent aphthous ulcers (RAU). Ten patients with multiple minor RAU participated in the study. The mean incidence of RAU was 17.8 during a 3-month period before the study. The patients used a dentifrice containing 1.2% SLS for a test period of 3 months followed by a dentifrice without SLS for the same time period. The results showed a statistically significant decrease in the number of aphthous ulcers from 14.3 after using the SLS-containing dentifrice to 5.1 ulcers after brushing with the SLS-free dentifrice (p < 0.05). It is suggested that the denaturing effect of SLS on the oral mucin layer, with exposure of the underlying epithelium, induces an increased incidence of RAU.

Desquamative effect of sodium lauryl sulfate on oral mucosa. A preliminary study.

Sodium lauryl sulfate (SLS) is the most commonly used detergent in dentifrices. The present study was concerned with the effect of SLS content of toothpastes on oral epithelial desquamation in an experimental model. Ten dental hygiene students participated in this double-blind cross-over study. Five dentifrices with different concentrations of SLS (ranging from 0.0% to 1.5%) were used in randomized order in the study. One centimeter of each test dentifrice was applied in a cap-splint, which covered both attached and non-attached oral mucosa of the upper jaw for 2 min twice daily. The test period for each experimental dentifrice was 4 days, followed by a 10-day rest period. The dentifrice without SLS did not result in any onward reaction, whereas the dentifrice containing 1.5% SLS provoked desquamation in 60% of the subjects.