The dynamics of the oesophageal squamous epithelium 'normalisation' process in patients with gastro-oesophageal reflux disease treated with long-term acid suppression or anti-reflux surgery.

BACKGROUND: Proton pump inhibitors and laparoscopic anti-reflux surgery (LARS) offer long-term symptom control to patients with gastro-oesophageal reflux disease (GERD). AIM: To evaluate the process of 'normalisation' of the squamous epithelium morphology of the distal oesophagus on these therapies. METHODS: In the LOTUS trial, 554 patients with chronic GERD were randomised to receive either esomeprazole (20-40 mg daily) or LARS. After 5 years, 372 patients remained in the study (esomeprazole, 192; LARS, 180). Biopsies were taken at the Z-line and 2 cm above, at baseline, 1, 3 and 5 years. A severity score was calculated based on: papillae elongation, basal cell hyperplasia, intercellular space dilatations and eosinophilic infiltration. The epithelial proliferative activity was assessed by Ki-67 immunohistochemistry. RESULTS: A gradual improvement in all variables over 5 years was noted in both groups, at both the Z-line and 2 cm above. The severity score decreased from baseline at each subsequent time point in both groups (P < 0.001, all comparisons), attaining a normal level by 5 years. Corresponding decreases in Ki-67 expression were observed (P < 0.001, all comparisons). No significant differences were found between esomeprazole treatment and LARS. Neither baseline severity score nor Ki-67 expression predicted the risk of treatment failure. CONCLUSIONS: Five years of treatment is generally required before squamous epithelial cell morphology and proliferation are 'normalised' in patients with chronic GERD, despite endoscopic and symptomatic disease control. Control of the acid component of the refluxate seems to play the predominant role in restoring tissue morphology.

Long-term feeding of sodium saccharin to nonhuman primates: implications for urinary tract cancer.

BACKGROUND: It was observed in the early 1970s that saccharin produced bladder cancer in rats. However, it has been unclear whether sodium saccharin when consumed by humans poses a substantial carcinogenic hazard. Numerous epidemiologic studies have not shown any evidence of increased urothelial proliferation associated with ingestion of sodium saccharin. PURPOSE: Our purpose was to determine the effects of long-term feeding of sodium saccharin to three species of nonhuman primates. METHODS: Twenty monkeys of three species (six African green, seven rhesus, six cynomolgus, and one hybrid [of rhesus male and cynomolgus female parentage]) were treated with sodium saccharin (25 mg in the diet/kg body weight daily for 5 days a week) beginning within 24 hours after birth and continuing for up to 24 years. Sixteen monkeys (seven rhesus and nine cynomolgus) served as controls. During their last 2 years of life, urine was collected from selected treated and control animals and evaluated for various urinary chemistries and for the presence of calculi, microcrystalluria, and precipitate. Urinary bladders were examined by light microscopy and by scanning electron microscopy. RESULTS: Sodium saccharin treatment had no effect on the urine or urothelium in any of these monkeys. There was no evidence of increased urothelial cell proliferation, and there was no evidence of formation of solid material in the urine. CONCLUSION: Although the dose of sodium saccharin administered to these monkeys was only five to 10 times the allowable daily intake for humans, the results provide additional evidence that sodium saccharin is without a carcinogenic effect on the primate urinary tract.

A randomized comparative study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.

AIM: To assess the efficacy of the 8-week therapy with esomeprazole 40 mg vs. pantoprazole 40 mg for healing erosive oesophagitis (EE) as part of a management study. METHODS: Patients had a history of gastro-oesophageal reflux disease symptoms (> or =6 months) and had suffered heartburn on at least 4 of the 7 days preceding enrollment. Endoscopies were performed to grade EE severity using the Los Angeles (LA) classification system at baseline, 4 and 8 weeks (if unhealed at 4 weeks). Heartburn severity was recorded by patients on diary cards. The primary end point was healing of EE by week 8 of treatment. RESULTS: Of 3170 patients randomized, the intent-to-treat population consisted of 3151 patients (63% male, mean age: 50.6 years, 27% Helicobacter pylori-positive). Esomeprazole 40 mg healed a significantly greater proportion of EE patients than pantoprazole 40 mg at both 4 weeks (life table estimates: esomeprazole 81%, pantoprazole 75%, P < 0.001) and 8 weeks (life table estimates: esomeprazole 96%, pantoprazole 92%, P < 0.001). The median time to reach sustained heartburn resolution was 6 days in patients receiving esomeprazole and 8 days with pantoprazole (P < 0.001). CONCLUSION: Esomeprazole 40 mg is more effective than pantoprazole 40 mg for healing EE and providing resolution of associated heartburn.

Esomeprazole 20 mg vs. pantoprazole 20 mg for maintenance therapy of healed erosive oesophagitis: results from the EXPO study.

BACKGROUND: Following initial healing of erosive oesophagitis, most patients require maintenance therapy to prevent relapse. AIM: To compare endoscopic and symptomatic remission rates over 6 months' maintenance therapy with esomeprazole or pantoprazole (both 20 mg once daily) in patients with healed erosive oesophagitis. METHODS: Patients with symptoms of gastro-oesophageal reflux disease and endoscopically confirmed erosive oesophagitis at baseline were randomized to receive esomeprazole 40 mg or pantoprazole 40 mg for up to 8 weeks. Patients with healed erosive oesophagitis and free of moderate/severe heartburn and acid regurgitation at 4 weeks or, if necessary, 8 weeks entered the 6-month maintenance therapy phase of the study. RESULTS: A total of 2766 patients (63% men; mean age 50 years) received esomeprazole 20 mg (n = 1377) or pantoprazole 20 mg (n = 1389) and comprised the intention-to-treat population. Following 6 months of treatment, the proportion of patients in endoscopic and symptomatic remission was significantly greater for those receiving esomeprazole 20 mg (87.0%) than pantoprazole 20 mg (74.9%, log-rank test P < 0.0001). Esomeprazole 20 mg produced a higher proportion of patients free of moderate to severe gastro-oesophageal reflux disease symptoms and fewer discontinuations because of symptoms than pantoprazole 20 mg (92.2% vs. 88.5%, P < 0.001). CONCLUSIONS: Esomeprazole 20 mg is more effective than pantoprazole 20 mg for maintenance therapy following initial healing of erosive oesophagitis and relief of gastro-oesophageal reflux disease symptoms.

Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: data from the SOPRAN and LOTUS studies.

BACKGROUND: Control of chronic gastro-oesophageal reflux disease may be achieved either by anti-reflux surgery (ARS) or by long-term medical therapy with proton pump inhibitors (PPIs). The primary efficacy results of the SOPRAN study, comparing long-term omeprazole use with open ARS, and the LOTUS study, comparing long-term esomeprazole use with laparoscopic ARS, have been reported. A secondary objective of these studies was to address the long-term safety of these respective therapeutic strategies and thereby provide a valid scientific platform for assessing long-term PPI safety. AIM: To assess the safety of long-term PPI therapy with omeprazole and esomeprazole through analyses of data from the randomised SOPRAN and LOTUS studies. METHODS: Safety data were collected from patients during the 12-year period of the SOPRAN study (n = 298) and the 5-year period of the LOTUS study (n = 514). Reported serious adverse events (SAEs) and changes in laboratory variables were analysed. RESULTS: Across both studies, SAEs were reported at a similar frequency in the PPI and ARS treatment groups. Taking the time frames into consideration, the number of fatal SAEs in the two studies was low in both treatment groups. Laboratory results, including routine haematology and tests for liver enzymes, electrolytes, vitamin D, vitamin B12 , folate and homocysteine, showed no clinically relevant changes over time. As expected, gastrin and chromogranin A were elevated in the PPI groups, with the greatest increases observed in the first year. CONCLUSION: No major safety concerns arose during 5-12 years of continuous PPI therapy. (ClinicalTrials.gov: NCT00251927 and NCT00256737).

The enteric nervous system participates in the secretory response to the heat stable enterotoxins of Escherichia coli in rats and cats.

Intestinal secretion was evoked in periarterially denervated jejunal segments of anesthetized rats and cats by exposing the intestines to the heat stable (ST) toxins from a strain of Escherichia coli producing both STa and STb toxins. The secretion was significantly inhibited and to about the same relative extent by the addition of each one of the three following drugs: hexamethonium (i.v., rats), lidocaine (applied on the serosal surface, rats) and tetrodotoxin (intra-arterial, cats). Atropine inhibited fluid secretion in some experiments. It is proposed that a nervous mechanism is mediating part of the secretory response to Escherichia coli heat stable toxins, since three different drugs, which influence nervous activity in different ways, significantly diminished the secretory response. A model for the secretory nervous reflex(es) within the enteric nervous system is proposed; Escherichia coli heat stable toxins activate a "receptor cell" in the epithelium, which then stimulates surrounding dendritic nerve endings via the release of unknown substance(s). A nicotinic receptor is involved but further characteristics of the nervous reflex(es) remain to be elucidated.

Neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide- induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.

Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[-4-(-5-nitro-2-furyl)-2- thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.

neu is not involved in N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced bladder carcinoma or 2-amino-4-(5-nitro-2-furyl)thiazole transformation of rat bladder epithelial cells.

Enhanced c-erbB-2/neu expression has been linked with a poor prognosis in human bladder cancer. Previous reports have shown that a point mutation at nucleotide T2012 in the coding region of the transmembrane domain of the rat gene is sufficient to confer transformation potential on this gene. We examined the comparative levels of p185neu as well as the sequence around the hotspot (T2012) of the neu gene of rat bladder cells transformed by 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT) or established in culture from N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat bladder tumors. We concluded that increased p185neu expression did not correlate significantly with tumorigenicity. No alterations in nucleotide sequences of the neu gene were observed in either in vitro model.

A comparison of the effects of sodium saccharin in NBR rats and in intact and castrated male F344 rats.

High doses of sodium saccharin (NaSac) increase proliferation in the bladder of the rat, with a male preponderance. The possibility that alpha 2u-globulin is involved in its mechanism of action was evaluated by feeding it at 7.5% of the diet to NCI-Black-Reiter (NBR) male rats, which do not synthesize liver-derived alpha 2u-globulin. NaSac affected urinary parameters similarly in F344 and NBR male rats, but NBR rats consumed more water leading to greater urinary volume. NaSac produced less proliferation in NBR than in intact F344 rats, with intermediate changes in castrated F344 males, which had intermediate urinary alpha 2u-globulin levels.

The influence of irradiation time per treatment session on acute and late skin reactions: a study on human skin.

A comparison of the radiation effect of altering the treatment time per session in fractionated radiotherapy was performed on human skin with 12 MeV electrons. Four fractions of 7.2 Gy were given within 22 days, once a week. The dose per fraction was administered in 4 min and 32 min, respectively. The dose rate was about 2 Gy/min and the prolonged treatment time was achieved by dividing each dose fraction into three equal subfractions with intervals of 14-15 min. Prolongation of the treatment time resulted in a significant reduction of the skin erythema (p less than 0.001), pigmentation (p less than 0.05) and the degree of telangiectasia at 5 years (p less than 0.001). The relative biological effectiveness (RBE) for the prolonged (32 min), in relation to that of the short (4 min) treatment time, RBE4 min/32 min, was 1.09-1.10 for erythema and 1.07-1.12 for telangiectasia. These findings indicate that prolongation of the treatment time per session has to be adjusted for in clinical radiation oncology.

Adverse events associated with hepatitis B vaccine in U.S. children less than six years of age, 1993 and 1994.

PURPOSE: This study evaluated infrequent adverse reactions to hepatitis B vaccine by investigating the association of this vaccine with adverse health outcomes for U.S. children less than six years of age. The evaluation of the association between hepatitis B vaccine and chronic arthritis provides needed data, relevant to the Institute of Medicine's Report that there are inadequate data available to assess the causal relationship of hepatitis B vaccine to arthritis risk. METHODS: The 1993 (n = 5505 children) and 1994 (n = 6515 children) National Health Interview Survey (NHIS) datasets were analyzed to provide post-marketing surveillance data from probability samples of the U.S. population. Incident cases of adverse events were determined from the temporal association between the hepatitis B vaccination and the adverse events. Logistic regression modeling was used to adjust for potential confounding. RESULTS: Controlling for age, race, and gender simultaneously in the 1994 NHIS, hepatitis B vaccine was found to be associated with prevalent arthritis [odds ratio (OR) = 5.91, 95% confidence interval (CI) = 1.05-33.14], incident acute ear infections (OR = 1.60, 95% CI = 1.00-2.58), and incident pharyngitis/nasopharyngitis (OR = 1.41, 95% CI = 0.95-2.09). CONCLUSIONS: Evidence from this study suggests that hepatitis B vaccine is positively associated with adverse health outcomes in the general population of US children.

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results.

INTRODUCTION: Esomeprazole, the first proton pump inhibitor to be developed as an optical isomer, has demonstrated more effective healing vs. omeprazole and lansoprazole in patients with reflux oesophagitis (RO). However, RO recurs in a high proportion (approximately 80%) of these patients within 12 months of initial therapy, highlighting the importance of maintenance treatment. Previous studies have shown esomeprazole to be effective as maintenance therapy in healed RO patients. AIM: This study was conducted to compare esomeprazole 20 mg once daily (o.d.) with lansoprazole 15 mg o.d. for the prevention of recurrence of RO. METHODS: 1391 patients with endoscopically verified RO (LA classification) were enrolled in this randomized, double-blind, parallel-group, multicentre trial. During the initial healing phase of the study, all patients received 4-8 weeks' open treatment with esomeprazole 40 mg: 1236 healed (identified by endoscopy at 4 and 8 weeks) and symptom-free (i.e. no heartburn or acid regurgitation) patients were randomized to 6 months' maintenance treatment with esomeprazole 20 mg o.d. or lansoprazole 15 mg o.d. Time to relapse (relapse of RO and/or discontinuation due to symptom recurrence) was analysed using a log-rank test. RESULTS: Esomeprazole maintained a significantly higher proportion of patients in remission than lansoprazole over the 6-month course of treatment (P < 0.0001, intention-to-treat analysis). After 6 months' treatment, 83% of esomeprazole recipients were in remission compared with 74% of lansoprazole recipients (life-table estimates). Esomeprazole gave a longer time to relapse than lansoprazole irrespective of baseline LA Grade, significantly so for baseline LA Grades B, C and D (P < 0.05 for each comparison). Significantly more patients were free from heartburn in the esomeprazole group compared with the lansoprazole group at 1, 3 and 6 months (P < 0.05). Significant differences at 6 months between esomeprazole 20 mg o.d. and lansoprazole 15 mg o.d. were also observed for control of epigastric pain and acid regurgitation (P < 0.05 and P < 0.001, respectively). Both treatment regimens were well tolerated. CONCLUSION: Esomeprazole 20 mg o.d. is a more effective maintenance treatment than lansoprazole 15 mg o.d. for symptom-free patients with healed RO.

Esomeprazole 20 mg and lansoprazole 15 mg in maintaining healed reflux oesophagitis: Metropole study results.

AIM: To compare the efficacy of esomeprazole, 20 mg once daily, vs. lansoprazole, 15 mg once daily, for the maintenance treatment of patients with healed reflux oesophagitis. METHODS: During the initial open healing phase, 1391 patients with endoscopically verified reflux oesophagitis and a history of heartburn, with or without acid regurgitation, received esomeprazole 40 mg for 4-8 weeks. Patients who were healed (identified by endoscopy at 4 or 8 weeks) and symptom free were then randomized to receive 6 months of treatment with esomeprazole, 20 mg once daily, or lansoprazole, 15 mg once daily. RESULTS: Esomeprazole, 20 mg once daily, maintained a significantly higher proportion of patients in remission than lansoprazole, 15 mg once daily, over 6 months [83% (95% CI, 80-86%) of esomeprazole recipients compared with 74% (95% CI, 70-78%) of lansoprazole recipients; P < 0.0001; life table estimates]. When data were analysed according to baseline Los Angeles grade classification, esomeprazole, 20 mg once daily, achieved consistently higher remission rates across all grades of disease severity, whereas the efficacy of lansoprazole decreased to a greater extent with increasing severity of reflux oesophagitis. CONCLUSION: Esomeprazole, 20 mg once daily, is more effective than lansoprazole, 15 mg once daily, in maintaining remission in patients with healed reflux oesophagitis.

Age differences and changes in midline-crossing inhibition in the lower extremities.

BACKGROUND: The effects of crossing the body midline on the lower extremities of individuals 65 years of age and older was investigated. METHODS: The subjects were 10 individuals 65-79 years of age, 10 individuals 80 years and older, and 10 individuals 20-35 years. The total testing phase consisted of 2 sets of 30 trials per leg on 2 days. The subjects performed trials that involved movements ipsilaterally, contralaterally, and directly in front of the anterior superior iliac crest of the leg being tested. Reaction time and movement time scores were recorded. RESULTS: Individuals 65 years of age and older were found to exhibit slower reaction times to movements in a contralateral direction when compared with movements made in the ipsilateral direction whereas individuals 80 years of age and older were also found to exhibit slower reaction times to movements in a contralateral direction when compared with movements made in the midline and ipsilateral direction. CONCLUSIONS: These findings indicate that the effects of midline-crossing inhibition on the lower extremities reemerge in individuals 65 years and older, whereas in early development this effect disappears by 8 or 9 years of age.

Effects of cholera toxin, Escherichia coli heat stable toxin and sodium deoxycholate on neurotensin release from the ileum in vivo.

Neurotensin (NT) is a biologically active peptide found in specialized epithelial cells (N-cells) in the distal small intestine. In this study we tested the hypothesis that NT may be released by luminal secretagogues, i.e., cholera toxin, Escherichia coli heat-stable toxin and sodium deoxycholate. Cholera toxin elicited net fluid secretion in anesthetized cats. This secretion was accompanied by an increased release of NT-like immunoreactivity (NTLI) into the mesenteric vein when NTLI was measured with either a C-terminally or a N-terminally directed antibody. An increasing plasma NTLI concentration (N-terminally directed antibody) was recorded in the mesenteric vein and femoral artery in cholera experiments. These results indicate that cholera toxin releases NT from the small intestine. Since neurotensin causes intestinal fluid secretion at least in part via an activation of enteric nerves we propose that the N-cell functions as a 'receptor cell' which activates an intramural secretory reflex upon luminal stimulation by cholera toxin. This study does not support a similar role for NT in the secretion elicited by the heat stable toxin of Escherichia coli or by sodium deoxycholate since we were unable to demonstrate any intestinal release of NTLI after exposing the intestine to these secretory agents.

Streptococcus mutans levels and biotypes in Egyptian and Saudi Arabian students during the first months of residency in the United States.

Several studies indicated that serotype/biotype c strains are the most common on a global basis, but that regional differences may occur relative to other serotype/biotypes. Of particular interest is the observation that individuals residing in the Middle East have higher incidences of serotype e and d strains relative to their levels in American citizens. This could reflect exposure to different Streptococcus mutans serotypes during the period in which the teeth are colonized, or might reflect other factors local to the region, such as diet. The purpose of the present study was to observe Egyptian and Saudi Arabian students during the first four months after their arrival in the United States, in order to determine whether this change in habitat affected the levels and biotypes of S. mutans. The results of this study showed that biotype c strains were the most prevalent in saliva and plaque of these Egyptians and Saudi Arabian students, followed by biotype e and biotype d. There was a drop in the number of S. mutans in the saliva and the proportions of S. mutans in the plaque after two months of residence in the United States, followed by a significant increase after four months of residence. This increase was most noticeable in subjects who had a higher number of decayed surfaces. In these subjects, the percentage of S. mutans in pooled occlusal plaque increased significantly, from 6.1 to 13.2%.

Dental benefits of limited exposure to fluoridated water in childhood.

The effect of limited exposure to fluoridated water in childhood is of potential importance in highly-mobile modern society, but the subject has not been well-studied. This longitudinal study assessed caries experience and S. mutans proportions from fissure plaque in school-children who lived for at least the three years of the study in a non-fluoridated community (0.2 mg/L). Residence histories permitted division of the cohort into those who had lived all their lives in non-fluoridated communities, and those who had lived for some time previously in a fluoridated community. The children were aged 6-7 years at the beginning of the three-year study. Children with previous residence in the fluoridated communities developed 26.8% less caries in their permanent teeth during the study than did the children who had lived in non-fluoridated communities all their lives (p = 0.04), and had 29.8% less caries after three years (p = 0.02). Differences between the groups in S. mutans proportions from fissure plaque, sampled at six-monthly intervals throughout the study, could not be demonstrated. The dental benefits observed could not be attributed to socio-economic differences between the groups. Despite evidence that the benefits of limited ingestion of fluoridated water are topical in nature, the fact that many of the affected teeth in this study were unerupted at the time of the fluoride exposure means that pre-eruptive benefits cannot be ruled out.

Root caries in an optimally fluoridated and a high-fluoride community.

The purpose of this study was to measure the prevalence and distribution of root caries in two New Mexico communities. One community, Deming, had a natural fluoride concentration of 0.7 mg/L in its drinking water, optimum for its climate. The other, Lordsburg, was naturally fluoridated at 3.5 mg/L, five times the optimum. Dental examinations were carried out on 151 adults in Deming (mean age, 39.8 years) and 164 in Lordsburg (mean age, 43.2 years); only persons born in the communities were included. Prevalence of root caries was 23.8% in Deming and 7.3% in Lordsburg; mean number of lesions was 0.69 in Deming and 0.08 in Lordsburg (p less than 0.0001). Although there was more gingival recession in Lordsburg, Root Caries Index scores were five times greater in Deming. Root caries was more prevalent in older age groups, and was correlated with coronal caries experience in both communities. Root caries was correlated with plaque and calculus scores in Deming only. Logistic regression showed that city of residence was the major predictor of root caries, with other significant predictors being age, education, gingival recession, and loss of periodontal attachment. When combined with previous research, these results confirm that root caries experience is directly related to the fluoride concentration in the drinking water.

Sugared soda consumption and dental caries in the United States.

Because of the complexity of the caries process, the potential cariogenicity of specific food items is difficult to assess. The purpose of this study was to investigate the associations between sugared soda consumption and caries. Dietary and dental examination data from the 1988-94 Third National Health and Nutrition Examination Survey (NHANES III) were used. From the food frequency questionnaire and 24-hour recall data, significant associations between DMFS and soda consumption were generally seen in persons over age 25. No differences in DMFS, relative to soda consumption, were seen in persons under age 25, or in analyses of dfs for children under age 12. The observed associations could be due to the cumulative effects of the long-term consumption of sugared soda. The absence of apparent effects of sugared soda consumption in younger people may also be related to the increased use of fluorides since the 1960s.

The effects of sugars intake and frequency of ingestion on dental caries increment in a three-year longitudinal study.

A three-year longitudinal study was carried out with a group of children, initially aged 11-15, residing in non-fluoridated rural communities in south-central Michigan. This report analyzes the relation between caries increment and consumption of sugars from all sources to see if accepted relationships have changed with the caries decline in the United States. There were 499 children who provided three or more 24-hour dietary recall interviews, and who received dental examinations at baseline and after three years. Caries increment averaged 2.91 DMFS over the three years, with 81% of new lesions on pit-and-fissure surfaces. Consumption of sugars from all sources averaged 156 g per day for males and 127 g per day for females, an average of 52 kg per person per year. Sugars constituted one-quarter of total caloric intake for both boys and girls, and the average number of eating occasions per day was 4.3. Children who consumed a higher proportion of their total energy intake as sugars had a higher increment of approximal caries, though there was little relation to pit-and-fissure caries. The average number of daily eating occasions was not related to caries increment, nor was the average number of sugary snacks (defined as foods with 15% or more of sugars) consumed between meals, but the average consumption of between-meal sugars was related to the approximal caries increment. When children were categorized by high caries increment compared with no caries increment, a tendency toward more frequent snacks was seen in the high-caries children.(ABSTRACT TRUNCATED AT 250 WORDS)