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Linda Book

Publications and source records attributed to Linda Book.

7 recordsLinked to original sources

Multicenter, randomized, double-blind study comparing 20 and 40 mg of pantoprazole for symptom relief in adolescents (12 to 16 years of age) with gastroesophageal reflux disease (GERD).

An age-appropriate questionnaire (GASP-Q) was used to assess the frequency and severity of the gastroesophageal reflux disease (GERD) symptoms: abdominal/belly pain, chest pain/heartburn, pain after eating, nausea, burping/belching, vomiting/regurgitation, choking when eating, and difficulty swallowing, in adolescents age 12 to 16 years. The primary objective was to compare the mean composite symptom score (CSS) at week 8 with baseline after treatment with 20 or 40 mg of pantoprazole. Statistically significant (p < 0.001) improvement in CSS occurred in both groups. Safety was comparable between the 2 groups. Pantoprazole was safe, well tolerated, and effective in reducing symptoms of GERD in adolescents.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Prevalence of celiac disease among relatives of sib pairs with celiac disease in U.S. families.

OBJECTIVE: Celiac disease is a familial malabsorptive disorder with an estimated prevalence in first-degree relatives of 10-12%. The prevalence for first-degree and more distant relatives has not been determined in families where there are two affected first-degree relatives. The aim of our investigation was to estimate the prevalence and relative risk for celiac disease in relatives of two siblings diagnosed with celiac disease. METHODS: We ascertained sib pairs with celiac disease, and then identified all living first-degree relatives and available second-degree relatives to minimize ascertainment bias. We measured IgA endomysial antibodies, a highly specific and sensitive assay for celiac disease, in all subjects without a confirmed biopsy diagnosis. For those individuals with positive serologic tests, IgA tissue transglutaminase antibody tests and human leukocyte antigen DQA1 and DQB1 genotyping were performed for additional confirmation. Individuals with positive biopsy and/or serology were considered affected. We calculated the relative risk of being affected with celiac disease using the lambda(R) statistic. RESULTS: The prevalence of celiac disease in relatives of affected sib pairs was as follows: 21.3% (13/61) of siblings (lambda(S) = 53); 14.7% (10/68) of offspring (lambda(O) = 37); 17.2% (28/163) of first-degree relatives; 19.5% (16/82) of second-degree relatives; and 17.8% (52/292) of all relatives (lambda(R) = 44.5). CONCLUSIONS: In these families, we identified a sibling risk approximately double that found in previous reports, as well as significant risk for more distant relatives, probably because of sharing of a common gene. In families where at least two siblings have been diagnosed with celiac disease, relatives are at high risk for celiac disease. Screening should be considered for all family members.

Autoantibodies↗

Genome-wide linkage analysis for celiac disease in North American families.

Celiac disease (CD) is an autoimmune disease caused by sensitivity to the dietary protein gluten. It has a prevalence of 1 in 250 in the United States. Multiple-case families are common with a risk to siblings from 10-12%. Previous linkage studies have found no significant evidence for linkage other than to HLA. In this study, we performed a genome-wide search on 62 families with at least two cases of CD to identify non-HLA loci for CD. Two-point and multipoint parametric and nonparametric analyses were performed on the entire set of families and on sets stratified by the HLA genotype. Accounting for multiple testing, we found genome-wide intermediate linkage evidence at 18q (heterogeneity LOD (HLOD) = 3.6) and at 3p (HLOD = 3.2) and suggestive evidence at 5p (HLOD = 2.7). Good consensus between two-point and multipoint evidence was not found, and after genotyping with new markers in these regions, our results were inconclusive. The 18q region had intermediate two-point evidence, but weak multipoint evidence. At 3p and 5p, the addition of follow-up markers added flanking support, yet multipoint evidence was still lacking. Our results indicate that multipoint analyses may be hindered by the complexity of CD. Multipoint analyses are not robust to model misspecification, and further development of models is needed. Additional study of these and other families is necessary to validate or rule out the regions implicated in this study.

Antibody Specificity↗

Efficacy of lansoprazole in the treatment of gastroesophageal reflux disease in children.

OBJECTIVES: To assess the efficacy of lansoprazole for the relief of symptoms due to gastroesophageal reflux disease (GERD) in children 1 to 11 years of age. In addition, the efficacy in healing of erosive esophagitis (EE) was determined in those children with EE who were enrolled in the study. METHODS: In this phase I/II, open-label, multicenter (11 sites) U.S. study, children with symptomatic GERD, EE by endoscopy, and/or intraesophageal pH < 4 for greater than 4.2% of the time based on 24-hour pH testing were assigned, on the basis of body weight, to lansoprazole 15 mg (< or = 30 kg) or 30 mg (> 30 kg) once daily for 8 to 12 weeks. At the discretion of the investigator, the dosage of lansoprazole was increased up to 60 mg daily in children who continued to be symptomatic after 2 weeks of treatment. Symptom response was assessed by investigator interview and daily diary. Esophagitis healing was evaluated by repeat endoscopy after 8 and, if applicable, 12 weeks of treatment. RESULTS: Sixty-six children were enrolled. At week 8, 78% (21/27) of the children with EE at baseline had healed; the remaining six children were healed by week 12 (100%, 6/6). By investigator interview, 70% of children experienced resolution or improvement in their overall symptoms of GERD by their final visit. Statistically significant reductions from baseline in the severity of each symptom were reported with the exceptions of wheezing, hematemesis, and melena. Based on daily diary data, improvement in overall GERD symptoms was reported in 76% (47/62) of all children. With few exceptions, significant (P < 0.05) reductions from baseline occurred during each of the 2-week treatment intervals of the study period in the percentage of days and the average daily severity of GERD symptoms, the percentage of days antacid was used, and the average number of antacid tablets used per day. CONCLUSION: In children 1 to 11 years of age, lansoprazole is efficacious in healing EE and in relieving GERD-related symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pharmacokinetics and pharmacodynamics of lansoprazole in children with gastroesophageal reflux disease.

OBJECTIVES: To evaluate the pharmacokinetics and pharmacodynamics of lansoprazole in children between 1 and 11 years of age with gastroesophageal reflux disease (GERD). METHODS: In a multicenter, open-label trial of pediatric patients with symptomatic GERD, children were assigned, based on their weight, to receive lansoprazole 15 mg (patients weighing < or = 30 kg) or lansoprazole 30 mg (patients weighing > 30 kg) once daily. The effects of lansoprazole on 24-hour median intragastric pH, the percentages of time intragastric pH was above 3 and 4, and pharmacokinetic parameters were assessed at the day-5 visit and compared to baseline. RESULTS: Sixty-six children were enrolled in the study. Mean lansoprazole C(max) values of 790.9 ng/mL and 898.5 ng/mL and T(max) values of 1.5 hours and 1.7 hours were observed in the < or = 30 kg and the > 30 kg body weight treatment groups, respectively. AUC0-24 values of 1707 ng x h/mL and 1883 ng x h/mL and T1/2 values of 0.68 hours and 0.71 hours were observed in the < or = 30 kg and > 30 kg lansoprazole body weight treatment groups, respectively. There was no statistical significant difference in AUC0-24 between the two groups (P = 0.2571). After 5 days of treatment lansoprazole produced significant increases in patients' 24-hour mean intragastric pH and the percentages of time intragastric pH was above 3 and 4 compared to baseline. CONCLUSION: The observed pharmacokinetic properties of lansoprazole in children between 1 and 11 years of age with GERD were similar to those previously observed in healthy adult subjects. Lansoprazole significantly increased the mean 24-hour intragastric pH and the percentages of time intragastric pH was above 3 and 4 when children were dosed with either 15 or 30 mg according to body weight.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pediatric celiac disease: clinicopathologic and genetic aspects.

Evaluation for celiac disease (CD), an autoimmune enteropathy triggered by grain proteins in wheat, barley, rye, and possibly oats, is a common indication for pediatric endoscopy and biopsy. Duodenal or jejunal biopsy remains key for the initial diagnosis of CD. Small intestinal pathology may be diffuse or focal in CD, and histologic findings are nonspecific and must be interpreted in conjunction with clinical and serologic findings. A standardized grading system for CD biopsies is recommended. This review article summarizes the epidemiology, clinical manifestations, genetics, pathogenesis, and serologic and histologic findings of CD. Clinical management of CD and general handling of small intestinal biopsies are also addressed.

Biopsy↗