A single dose of ranitidine 150 mg modulates oesophageal acid sensitivity in patients with functional heartburn.

BACKGROUND: The rapid onset and symptomatic response to histamine-2 receptor antagonists prior to the pharmacological effect on acid secretion suggests a different mechanism of action. AIM: To determine if ranitidine decreases oesophageal sensitivity to chemical and mechanical stimulation, potentially via oesophageal histamine receptors. METHODS: A total of 18 patients with functional heartburn received oral ranitidine 150 mg b.d. or placebo for 7 consecutive days in a double-blind randomized crossover design and underwent Barostat balloon distention and Bernstein acid infusion on study day 1 (90 min postdose) and study day 7. First sensation and pain were recorded and pain severity was rated on a 5-point Likert scale and a 100 mm visual analogue scale. Least square mean values were generated and one-tailed t-tests were performed. RESULTS: After a single dose of ranitidine 150 mg, time to pain with oesophageal acid infusion was increased by 29% (P < 0.05) and visual analogue scale and Likert scores were decreased by 20% (P < 0.06) and 23% (P < 0.02), respectively compared with placebo. After 1 week of ranitidine, positive alterations in sensory parameters persisted. Balloon distention sensory parameters were not altered by ranitidine. CONCLUSIONS: Ranitidine significantly decreased oesophageal sensitivity to acid. Failure of ranitidine to improve balloon sensory parameters supports existence of multiple sensory pathways in the oesophagus.

Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control.

BACKGROUND: Oesophageal acid neutralization with antacids depends on the duration of oesophageal antacid exposure and acid neutralizing capacity. A gum that releases antacid as it is chewed could take advantage of both mechanisms to enhance heartburn relief. METHODS: Twenty-four subjects were crossed over to four regimens: placebo, chewable antacid tablets (1000 mg CaCO3), lower dose gum (600 mg CaCO3) and higher dose gum (900 mg CaCO3). A dual pH probe was placed, subjects ate a standardized provocative meal and self-dosed once as needed. Symptoms were recorded every 15 min using visual analogue and Likert scales. SYMPTOMS: Both gums decreased heartburn compared to placebo for 120 min. Higher dose gum decreased heartburn more than chewable antacids up to 120 min post-dose. pH: Active chewable antacid and gums immediately increased oesophageal pH, with significant improvement 15-30 min post-dose. SUMMARY: (i) both gums promptly decreased heartburn and elevated oesophageal pH; (ii) both gums provided sustained relief for 120 min; (iii) antacid gums provided faster and more prolonged symptom relief and pH control than chewable antacids. CONCLUSIONS: Calcium carbonate gum effectively neutralizes oesophageal acidity and relieves symptoms following a meal, and is superior to chewable antacids in terms of the duration of heartburn relief.

Ioxilan, a third generation low osmolality nonionic contrast medium. Systemic and renal hemodynamic effects.

The choice between high cost, low toxicity nonionic contrast media (CM) and low cost ionic CM poses a dilemma for radiologists. Ioxilan, a third generation nonionic CM, is obtained by simple conversion from an ionic CM. To examine how this economically promising, low osmolality CM (570 mOsm at 300 mgI/ml) affects canine systemic and renal hemodynamics, IV bolus injections of 350 mgI/ml at 2 ml/kg of Iohexol and Ioxilan were compared. Satisfactory nephrograms and pyelograms were produced by both agents, without significant differences. The effects on systemic and renal hemodynamics were minimal and statistically equal for both CM. The acute systemic and renal responses and radiographic image quality of Ioxilan and Iohexol confirm that the two compounds are biologically equivalent, and that the novel molecular design employed in Ioxilan to achieve very low osmolality also provides good biological tolerance.

Statistical considerations related to intra-oral studies.

Intra-oral studies use caries models from which conclusions are drawn concerning the caries process in the clinical environment. Recently, attention has been drawn to the issue of proper analysis and interpretation of the data from such studies, with particular emphasis placed on a consideration of the role such studies can and should play as a component of product claim submissions to the American Dental Association (ADA). This presentation discusses a number of issues relevant to this consideration, including the validity and reliability of the intra-oral modeling process, the relationship between these concepts and the requirements imposed by the ADA Guidelines for superiority and equivalence claims, and a brief enumeration of several other statistical issues which ought to be considered in the handling of data from such studies.

Interim report of the ad hoc committee for the consideration of statistical concerns related to the use of intra-oral models in submissions for product claims approval to the American Dental Association.

Subsequent to the American Dental Association Symposium on Intra-oral Studies, held in Chicago in September, 1990, the Council on Dental Therapeutics decided that further consideration should be given to statistical issues relating to intra-oral models. The authors accepted the request of Council staff to assist in the development of Guidelines concerning the validity, reliability, and combinability of data obtained from these models. The ensuing work in this area, which began in the fall of 1990 and has continued to date, has thus far focused on the tissue of validity. The purpose of the present paper is to provide the interested community at large with an update on the progress made thus far, and to provide some perspective as to where all of the work in this area may eventually be leading. It is anticipated that a more comprehensive and definitive report will be produced at the completion of this process.

Effect of after-meal sucrose-free gum-chewing on clinical caries.

Previous in situ and in vitro studies have demonstrated that the chewing of sucrose-free gum after eating reduces the development of dental caries. To investigate the extrapolation of these findings to the clinical setting, we conducted a two-year study on 547 schoolchildren in Budapest, Hungary. Subjects in the "Gum" group were instructed to chew one stick of a commercially available sorbitol-sweetened chewing gum for 20 minutes after meals, three times daily. The "Control" group was not provided with chewing gum. After two years, the "Gum" group exhibited a 38.7% reduction in incremental caries, excluding white spots, compared with the "Control" group. Including white spots, a corresponding 33.1% reduction was indicated. These results clearly suggest that even in a moderate caries population practicing normal oral hygiene, including the use of fluoride dentifrices, an after-meal gum-chewing regimen can significantly reduce the rate of caries development.

Composition of plaque and saliva following use of an alpha-tricalcium-phosphate-containing chewing gum and a subsequent sucrose challenge.

Previous studies demonstrated that the chewing of a 2.5% (mass fraction) alpha-tricalcium-phosphate-fortified (alpha-TCP) experimental chewing gum released sufficient calcium and phosphate to eliminate any fall in the tooth mineral saturation of plaque fluid after a sucrose rinse (Vogel et al., 1998). In contrast, the chewing of a conventional sugar-free gum did not eliminate this decrease in saturation. The purpose of this study was to examine if the release of ions from plaque calcium-phosphate pools induced by this gum could provide protection during subsequent exposure to cariogenic conditions. Fourteen subjects accumulated plaque for 48 hrs, fasted overnight, chewed a control or experimental gum for 15 min, and subsequently rinsed 1 min with a mass fraction 10% sucrose solution. Before gum chewing, and at 7 min and 15 min afterward, whole plaque, plaque fluid, and salivary samples were obtained and analyzed by micro-analytical techniques. Additional samples were collected and analyzed at 25 min (7 min after the sucrose rinse). Although the results confirmed the deposition of large amounts of calcium and phosphates in plaque seen in the previous study, only a small increase was seen in plaque-fluid-free calcium and phosphate before sucrose administration. This suggests that few of the mineral ions were mobilized under non-cariogenic conditions. However, 7 min after the sucrose rinsing, an increase in these concentrations was seen which, based on hydroxyapatite ion activity product calculations, indicated a decrease in the driving force for demineralization compared with that seen with the control gum. These results suggest that the chewing of the experimental gum deposits a labile mineral reservoir in plaque that can resist a subsequent cariogenic challenge.

Composition of plaque and saliva following a sucrose challenge and use of an alpha-tricalcium-phosphate-containing chewing gum.

Calcium phosphate concentrations in plaque, plaque fluid, and saliva play an important role in caries prevention. In this study, we used a microanalytical technique to examine the anticaries potential of a 2.5% (mass fraction) alpha-tricalcium-phosphate-fortified experimental gum by measuring the pH, free and total calcium, and total phosphate in plaque fluid, whole plaque, and saliva, and centrifuged saliva from 14 subjects who (1) accumulated plaque for 48 hours, (2) fasted overnight, (3) rinsed for 1 min with sucrose, and (4) chewed a control or experimental gum for 15 min. From these data, the hydroxyapatite (HAp) ion activity products (IAP[HAp]) of saliva and plaque fluid were calculated as a measure of tooth mineral saturation. Results, compared with those of the control gum, show significant increases in pH and in free calcium and phosphate concentrations in plaque fluid and saliva when the experimental gum was chewed following sucrose ingestion. These increases result in a rise in fluid saturation with respect to tooth mineral that, for plaque fluid, nearly cancels the decrease seen with the control gum after the sucrose rinse. This suggests that the experimental gum may be more effective than a conventional gum in ameliorating the cariogenic effects of sucrose. Similar statistically significant increases were also seen in the total calcium content of the plaque fluid, centrifuged saliva, whole saliva, and whole plaque, and in the total phosphate of whole plaque and whole saliva. These results suggest that the deposition of a mineral reservoir in plaque and saliva by the experimental gum may help resist future cariogenic challenges.

Caries risk assessment in a longitudinal discrimination study.

Our objective was to develop and perfect a model for the assessment of risk of dental caries onset in children. Even though dental caries prevalence in children is continuing to decline, there is still a significant minority for whom it is a problem. In this study, we sought to ascertain whether a set of variables selected in a previous cross-sectional study could be used to differentiate between caries-free six-year-olds who would or would not subsequently present with clinically-detectable caries. A total of 472 caries-free six-year-olds--286 from a fluoridated community and 186 from a fluoride-deficient community--was selected. Clinical examinations for DMFS, dental fluorosis, and plaque were conducted. Stimulated whole saliva was collected for analysis of mutants streptococci, lactobacilli, total viable flora, and fluoride, calcium, and phosphate concentrations. A questionnaire was used for collection of demographic data as well as information on prior fluoride exposure, dietary habits, and oral hygiene practices. By means of linear discriminant analyses, it was possible to predict correctly which children would develop caries within six to 12 months (sensitivity) in 82.8% of cases and which children would not develop caries during that period (specificity) in 82.4% of cases.

Caries risk assessment by a cross-sectional discrimination model.

Although the prevalence of dental caries is continuing to decline, it still affects a majority of the US population and can be a serious problem for those afflicted. The objective of this project was to develop and perfect a model for assessment of risk of dental caries onset in children. In the first study, reported herein, a set of clinical, microbiological, biochemical, and socio-demographic variables was identified that distinguished, with an acceptable level of sensitivity and specificity, between children who had no previous caries experience and children who had high caries levels. A total of 313 children--age 12-15 years, 140 from a fluoridated community and 173 from a fluoride-deficient community--was selected on the basis of previous caries experience, either zero DMFS or high DMFS (> or = 6 in the fluoridated or > or = 8 in the fluoride-deficient community). Clinical exams for DMFS, dental fluorosis, and plaque were conducted. Stimulated whole saliva was collected for analysis of mutans streptococci, lactobacilli, total viable flora, and fluoride concentration. A questionnaire was used for collection of demographic data as well as information on prior fluoride exposure, dietary habits, and oral hygiene practices. By means of discriminant analyses, with use of seven key clinical and laboratory variables, it was possible for zero-DMFS subjects to e classified correctly (specificity) in 77.6% of cases in the fluoridated community and in 86.1% of cases in the fluoride-deficient community. High-caries subjects were classified as such (sensitivity) in 79.3% and 88.1% of cases, respectively.

Role of angiotensin II in renal hemodynamic functions during the initial stages of acute ureteral obstruction.

This investigation examines the role of Angiotensin II in renal hemodynamic functions during acute unilateral ureteral obstruction (UUO) in a dog model. An electro magnetic flow probe was utilized to assess renal blood flow while the arteriovenous extraction technique of technetium 99m DTPA was utilized for the assessment of changes in filtration fraction and glomerular filtration rate. The effects of Angiotensin II receptor blockade on renal hemodynamic functions during acute UUO was evaluated in six dogs and compared to acute ureteral obstruction without receptor blockade in seven dogs. Angiotensin II blockade with (Sar1, Thr8)-Angiotensin II during UUO led to a striking increase in renal blood flow that was significantly different in comparison to normalized values from UUO alone (+delta 63 +/- 17 vs. +delta 22 +/- 6% at 30 min; p less than 0.05). There were, however, no significant differences in the magnitude of the decrease in filtration fraction and glomerular filtration rate in comparison to UUO alone. This investigation demonstrates that Angiotensin II has an inhibitory effect on the initial increase in renal blood flow with acute UUO. The possibility of successful pharmacologic intervention in the setting of UUO can be examined using animal models similar to the one described here. Pharmacologic treatment in the setting of acute UUO in patients might permit better preservation of renal function.

Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone.

The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root planing on reducing probing depth (PD) and improving clinical attachment level (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled multi-center clinical trials (5 centers each) were conducted; pooled data are reported from all 10 centers (447 patients). At baseline, following 1 hour of scaling and root planing (SRP) in patients free of supragingival calculus, the chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study sites in active chip subjects received either CHX chip plus SRP or SRP alone (to maintain study blind). Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6 weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P < 0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/- 0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The proportion of patients who evidenced a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group (19%) compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and transient toothache, including pain, tenderness, aching, throbbing, soreness, discomfort, or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip. These multi-center randomized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis.

Evaluation of the reproducibility of rest activity of the anterior temporal and masseter muscles in asymptomatic and symptomatic temporomandibular subjects.

There is a general assumption that temporomandibular disorders and the pain and tenderness of mastication muscles may be caused by hyperactivity. Five asymptomatic men, five asymptomatic women, and five women with temporomandibular disorders participated in this study. Multiple examinations were performed to provide information concerning the reproducibility of the rest electromyographic signals. No significant differences between groups were noted. This study supports the contention that the mean rest activity in women with pain and dysfunction is less than or equal to that of sex-matched controls.

Immediate implantation of pure titanium implants into extraction sockets of Macaca fascicularis. Part I: Clinical and radiographic assessment.

Immediate implants have the advantages of few surgical exposures, short treatment time, and maintenance of alveolar bone height and width. The purpose of this study was to compare immediate implants with conventional implants (implants placed into ossified extraction sites) in adult monkeys. Forty-eight implants were placed and allowed to heal for a 6-month period. Following a 7-month loading period, the monkeys were sacrificed, and implant sections were evaluated histologically. Clinical and radiographic measurements showed few significant differences between immediate and control implants.

Immediate implantation of pure titanium implants into extraction sockets of Macaca fascicularis. Part II: Histologic observations.

The purpose of this study was to evaluate immediate implants with implants placed in ossified extraction (control) sites. Histologic observation of immediate and control implants showed similar levels of bone integration at the light microscopic level using ground-section and decalcified thin-section histologic methods. Both histologic methods provided similar information in relation to determination of hard and soft tissue components measured at the interface. The percentage of bone integration was similar in different anatomic regions of the oral cavity. Bone patterns peripheral to the interface region differed, suggesting that special consideration be given to implants placed in the posterior regions of the maxilla and mandible.

Xerostomia and associated factors in a community-dwelling adult population.

Xerostomia is the subjective sensation of dry mouth. Estimates on the occurrence of xerostomia in community-dwelling adults have ranged from 10% among persons over age 50 to 40% for persons over age 65. Virtually no data are available for persons under age 50. To begin to establish a database on the occurrence of xerostomia and factors associated with it, a cross-sectional assessment of self-reported symptoms and salivary function was conducted across a broad age-range of generally healthy community-dwelling adults. A convenience sample of 710 adults who ranged from 19 to 88 years of age was drawn from various sources in the greater-Rochester, New York area. Study volunteers were administered a standardized questionnaire on general and oral health, which included questions on the symptoms of xerostomia, and were provided an oral screening examination, which included measurement of unstimulated and stimulated whole saliva flow rates. Overall, the observed prevalence of xerostomia was 24% among females and 18% among males. While xerostomia was more commonly observed in women than men, this association was only clear after age 50. Xerostomia was associated with: use of medications with hyposalivatory side-effects; difficulty with dry foods; cracked lips; dry eyes; difficulty swallowing; and, among males, current cigarette smoking. Results indicated a tendency for salivary flow rates to be lower for older persons, particularly the stimulated flow rate. There was a tendency in the younger cohorts for flow rates to be lower among individuals who reported sensation of dry mouth than among those who did not. This tendency was not apparent among older persons, suggesting that younger persons may be more likely to experience symptoms of oral dryness when salivary flow was low while older persons may relate symptoms of dry mouth to a more complex constellation of factors where salivary flow is only one component. These findings need to be examined further.

Patient satisfaction in four types of dental practice.

There has been a significant growth in alternative types of dental practice. To determine satisfaction, patients were surveyed in urban private practices, a hospital dental clinic, a neighborhood health center, and a large group practice situated in a shopping center, using a 14-item survey and a 5-point rating scale. Patient satisfaction was related to the following factors in descending order: dentist, staff, efficiency, time-cost, and accessibility. Patients rated private practice most favorably for all factors with the exception of accessibility, which was rated highest for the shopping center practice. Patients rated the hospital least favorably for all factors with the exception of dentist, which was rated least favorably for the shopping center practice. Although private practices were the most favorably perceived, alternative types of practice were also highly rated and met specific patient needs. Satisfaction was greater for older patients, for patients with less education, and for white compared with black patients.

The effect of chewing sugar-free gum after meals on clinical caries incidence.

To determine the effect of chewing sugar-free gum on caries incidence, the authors conducted a randomized clinical study. A total of 1,402 children in Puerto Rico, in grades 5 through 7 at baseline, completed the study. They were randomized by classroom into a control group or chewing gum group; those in the gum group were instructed to chew sugar-free gum for 20 minutes after each of three meals a day. Clinical and radiographic evaluations were performed at baseline and after two and three years. The results show that all subjects and high-risk subjects, respectively, in the gum group developed 7.9 percent and 11.0 percent fewer decayed, missing or filled surfaces than subjects in the control group. Based on these findings, the authors concluded that chewing sorbitol-based sugar-free gum after eating significantly reduces the incidence of dental caries.

Statistical considerations related to a meta-analytic evaluation of published caries clinical studies comparing the anticaries efficacy of dentifrices containing sodium fluoride and sodium monofluorophosphate.

The comparison of the anticaries efficacy of dentifrices containing sodium fluoride (NaF) and sodium monofluorophosphate (SMFP) has recently been addressed through a meta-analysis of published head-to-head clinical trials. Such an analysis is used to provide an omnibus conclusion on the basis of summary information obtained from several individual studies. An important aspect of a meta-analysis is the determination of which studies from among those available in the relevant literature are to be incorporated into the calculations. The statistical literature provides several perspectives with respect to this issue. A recently-published meta-analysis by Johnson (1993) resulted in the conclusion that dentifrices containing NaF provide significantly lower caries increments than do those containing SMFP. However, a similar analysis utilizing studies identified by Volpe, Petrone & Davies (1993) suggests that no such significant difference exists. The resolution of such conflicting results rests on clinical judgment concerning the issue of study inclusion. The clinical significance of the results of both of these analyses was considered. Despite the differences in the analyses, both support the conclusion that dentifrices containing SMFP provide equivalent anticaries protection as do those containing NaF, in accordance with the standards established in the current American Dental Association Guidelines for the comparison of fluoride dentifrices.

Comparison of the anticaries efficacy of dentifrices containing fluoride as sodium fluoride or sodium monofluorophosphate.

The dominance of the marketplace by dentifrices containing fluoride as sodium monofluorophosphate and sodium fluoride has given rise to great academic and commercial interest regarding the comparison of those two fluoride species. Since the 1970's, several comparative clinical trials have been conducted to investigate the relative anticaries efficacy of dentifrices containing these two agents, generally giving rise to equivocal results. Recently, attention has been turned to investigative efforts which employ information derived from the collective body of relevant comparative clinical studies available in the literature to establish an omnibus conclusion concerning this issue. Beginning with the sign test of Beiswanger & Stookey (1989), and continuing through the meta-analyses of Johnson (1993) and Proskin (1993), this line of research remains vital today. The recent publication of two studies (Marks et al, 1994; Stephen et al, 1994) previously documented in the literature only in abstract form (Conti et al, 1993; Stephen et al, 1993) has given rise to the need for the present meta-analytic reconsideration of the available data. As in the previous meta-analyses, the quantitative results obtained depended on the studies which provided data for the calculations. However, as also indicated in previously-documented meta-analyses, the clinical interpretation of the results, which was based on the guidelines published by the American Dental Association (Council on Dental Therapeutics, 1988), did not vary according to study selection.(ABSTRACT TRUNCATED AT 250 WORDS)