Amazonia through time: Andean uplift, climate change, landscape evolution, and biodiversity.

The Amazonian rainforest is arguably the most species-rich terrestrial ecosystem in the world, yet the timing of the origin and evolutionary causes of this diversity are a matter of debate. We review the geologic and phylogenetic evidence from Amazonia and compare it with uplift records from the Andes. This uplift and its effect on regional climate fundamentally changed the Amazonian landscape by reconfiguring drainage patterns and creating a vast influx of sediments into the basin. On this "Andean" substrate, a region-wide edaphic mosaic developed that became extremely rich in species, particularly in Western Amazonia. We show that Andean uplift was crucial for the evolution of Amazonian landscapes and ecosystems, and that current biodiversity patterns are rooted deep in the pre-Quaternary.

Clinical trial: lansoprazole 15 or 30 mg once daily vs. placebo for treatment of frequent nighttime heartburn in self-treating subjects.

BACKGROUND: Frequent nighttime heartburn is common. Lansoprazole 15 mg is indicated for treatment of heartburn and other gastro-oesophageal reflux disease-related symptoms. AIM: To evaluate the efficacy and safety of lansoprazole in self-treating subjects with frequent nocturnal heartburn. METHODS: A total of 864 subjects with heartburn on >or=2 days/week over the past month were randomized to double-blind treatment with lansoprazole 15 or 30 mg or placebo each morning. Endpoints were percentage of night times without heartburn (primary), percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1. RESULTS: Mean percentage of night times without heartburn was significantly greater with lansoprazole 15 mg (61.3%) or lansoprazole 30 mg (61.7%) vs. placebo (47.8%) over 14 days (P < 0.0001 vs. placebo for both doses). Percentage of 24-h days without heartburn and percentage of subjects without heartburn on day 1 were significantly greater with lansoprazole 15 or 30 mg vs. placebo. CONCLUSIONS: Both lansoprazole 15 and 30 mg were highly effective and well tolerated in reducing symptoms in subjects with frequent nighttime heartburn. The benefit of therapy on 24-h heartburn and nighttime heartburn on day 1 of treatment was also evident. Lansoprazole 15 mg is a suitable choice for management of frequent nighttime heartburn.

Oral pantoprazole in the form of granules or tablets are pharmacodynamically equivalent in suppressing acid output in patients with gastro-oesophageal reflux disease and a history of erosive oesophagitis.

AIM: To demonstrate the pharmacodynamic comparability between oral 40 mg pantoprazole delayed-release granules and tablets. METHODS: This was a multicentre, randomized, open-label, 2-period, 2-sequence, 9-week crossover study in patients aged 18-65 years with gastro-oesophageal reflux disease and documented erosive oesophagitis. The primary endpoint was a comparison of the inhibition of pentagastrin-stimulated maximum acid output (MAO) at steady state after once daily dosing for 1 week and 23 h after the last dose of pantoprazole granules and tablets. Basal acid output was measured prior to MAO. Standard safety evaluations were performed. The one-sided t-test was used to test the null hypothesis that granules - 1.2 x tablet >/= 0 against the alternative hypothesis that this difference was <0 for both MAO and basal acid output values. RESULTS: Sixty patients completed the study. The mean MAO values were 7.11 +/- 4.98 and 7.29 +/- 4.77 mmol/h, while the mean basal acid output values were 0.74 +/- 0.91 and 0.58 +/- 0.63 mmol/h for the granules and tablets, respectively. The two formulations were shown statistically to be pharmacodynamically equivalent in suppressing MAO (P = 0.006), safe and well tolerated. CONCLUSION: Patients with gastro-oesophageal reflux disease who are unable to swallow the tablet may safely be prescribed the pantoprazole sodium granules.

Efficacy of a motilin receptor agonist (ABT-229) for the treatment of gastro-oesophageal reflux disease.

BACKGROUND: ABT-229 is a potent motilin agonist without significant antibiotic activity. It has been shown to improve gastric emptying in humans and to increase lower oesophageal sphincter pressure in cats. AIM: To assess the efficacy of four different doses of ABT-229 (1.25 mg, 2.5 mg, 5 mg, 10 mg b.d.) compared to placebo in the treatment of gastro-oesophageal reflux disease, and to determine its safety in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, multicentre study, 324 patients with heartburn were randomized to receive four different doses of ABT-229 or placebo for 8 weeks. The efficacy was evaluated by Patient Symptom Questionnaire, daily diary, endoscopy and global evaluation of efficacy. RESULTS: There were no statistically significant improvement scores for any of the ABT-229 treatment groups vs. the placebo group in any of the efficacy parameters. Reflux symptom scores were significantly worse after treatment in the dyspeptic group. ABT-229 appeared to be well tolerated and safe in total daily doses up to 20 mg. CONCLUSION: ABT-229 appears to have limited, if any, clinical utility in the treatment of gastro-oesophageal reflux disease.

Efficacy and safety of sodium phosphate tablets compared with PEG solution in colon cleansing: two identically designed, randomized, controlled, parallel group, multicenter phase III trials.

BACKGROUND: Liquid purgatives for cleansing before colonoscopy often are poorly tolerated. A sodium phosphate tablet has been developed to provide equivalent efficacy with better patient tolerance. These 2 studies compare the safety, efficacy, and patient acceptance of the tablet (Visicol) to a polyethylene glycol (PEG) solution in adults undergoing colonoscopy. METHODS: Two identically designed, randomized, investigator-blinded, multicenter trials were performed. The primary efficacy variable was the overall quality of colon cleansing. Patient tolerance was assessed in terms of compliance with the dosing regimen. Safety assessments included recording of adverse events and changes in biochemical tests, electrocardiogram, and vital signs. RESULTS: Eight hundred forty-five patients participated in the studies; 420 took sodium phosphate tablets and 425 took a PEG solution. The 2 methods of preparation were equivalent in the overall quality of colon cleansing, cleansing in the right colon, and the frequency of inadequate preparation. Overall cleansing was excellent or good in 84.3% of patients in the tablet group and in 76.7% in the PEG group. Patient compliance was greater in the tablet group. There were also significantly fewer GI side effects in this group. CONCLUSIONS: Sodium phosphate tablets, compared with PEG solution, produce equivalent colon cleansing, are associated with fewer GI side effects, and are better tolerated by patients.

Double-blind placebo-controlled multicentre studies of rebamipide, a gastroprotective drug, in the treatment of functional dyspepsia with or without Helicobacter pylori infection.

BACKGROUND: Functional dyspepsia is a problem that is difficult to treat in clinical practice. AIM: To evaluate the efficacy and safety of rebamipide (a cytoprotective drug) in functional dyspepsia. METHODS: Patients with functional dyspepsia (n=557) were divided a priori into two studies by Helicobacter pylori status, and enrolled in a 2-week baseline evaluation period. Ninety-nine patients with Helicobacter pylori and 173 patients without Helicobacter pylori, continuing to have at least moderate upper abdominal pain or discomfort, were randomly assigned to rebamipide 100 mg, rebamipide 200 mg or placebo, three times a day, in a double-blind design for 8 weeks. RESULTS: There was significant improvement of individual symptom scores from baseline in all the treatment arms. No significant improvement of individual symptom scores was observed in either rebamipide group at the end of the studies compared to placebo, although the belching score was significantly reduced in the rebamipide 100 mg and 200 mg groups at week 2 (P=0.017 and P=0.012, respectively) in the Helicobacter pylori-positive patients. The ratio of patients who requested usage of the study medication again was greater in the rebamipide 100 mg (85%) and 200 mg (96%, P=0.020) groups compared with the placebo group (72%) among Helicobacter pylori-positive patients. There were no serious study medication related adverse events. CONCLUSIONS: Rebamipide was not superior to placebo in terms of individual symptoms at the end of treatment.

Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomised, double blind, placebo controlled trial.

INTRODUCTION: Erythromycin, a motilin agonist, is a potent prokinetic. ABT-229 is a specific motilin agonist that dose dependently accelerates gastric emptying. Dyspepsia and gastroparesis are common problems in type 1 diabetes mellitus. We aimed to evaluate the efficacy of ABT-229 in symptomatic diabetic patients with and without delayed gastric emptying. METHODS: Patients with type 1 diabetes and postprandial symptoms were randomised (n=270). Based on a validated C(13) octanoic acid breath test, patients were assigned to either the delayed or normal gastric emptying strata. Patients received one of four doses of ABT-229 (1.25, 2.5, 5, or 10 mg twice daily before breakfast and dinner) or placebo for four weeks following a two week baseline. A self report questionnaire measured symptoms on visual analogue scales; the primary outcome was assessment of change in the total upper abdominal symptom severity score (range 0-800 mm) from baseline to the final visit. RESULTS: The treatment arms were similar regarding baseline characteristics. There was symptom improvement on placebo and a similar level of improvement on active therapy for the upper abdominal discomfort severity score (mean change from baseline -169, -101, -155, -143, and -138 mm for placebo, and 1.25, 2.5, 5, and 10 mg ABT-229, respectively, at four weeks by intent to treat). The results were not significantly different in those with and without delayed gastric emptying. The severity of bloating, postprandial nausea, epigastric discomfort, heartburn, and acid regurgitation worsened dose dependently in a greater number of patients receiving ABT-229 than placebo. Overall, 63% of patients on placebo reported a good or excellent global response, and this was not different from the active treatment arms. CONCLUSIONS: The motilin agonist ABT-229 was not efficacious in the relief of postprandial symptoms in diabetes mellitus in the presence or absence of delayed gastric emptying.

Rabeprazole is superior to ranitidine in the management of active duodenal ulcer disease: results of a double-blind, randomized North American study.

OBJECTIVE: The primary purpose of this study was to compare the efficacy and tolerability of rabeprazole versus ranitidine in the treatment of patients with active duodenal ulcer disease. METHODS: This multicenter, double-blind, randomized, parallel-group study enrolled 376 patients. Patients were randomly assigned to receive rabeprazole 20 mg administered once daily in the morning (q.a.m.) with matching ranitidine placebo twice daily (b.i.d.) (n = 188), or ranitidine 150 mg b.i.d. with matching rabeprazole placebo q.a.m. (n = 188). Three visits were scheduled: wk 0 (baseline; days -3 to -1), wk 2 (day 15+/-3 days), and wk 4 (day 29+/-3 days). The primary efficacy response variable was defined as complete regeneration of the mucosa at the site of all ulcers identified during the study. Secondary efficacy variables included patients' ratings of frequency and severity of ulcer pain, frequency of antacid use, and improvement of overall physical well-being. Tolerability was evaluated with analyses of adverse events, laboratory evaluations, fasting serum gastrin levels, vital signs, body weight, and electrocardiograms. RESULTS: Up to 4 wk of treatment with rabeprazole 20 mg q.a.m. produced significantly greater healing rates, compared to treatment with ranitidine 150 mg b.i.d. (83% vs 73%; p = 0.017). Significant differences between treatment groups were also observed for secondary efficacy indices. At wk 2, rabeprazole was more likely than ranitidine to produce complete resolution of duodenal ulcer pain (39% vs 25%; p = 0.006), improvement in duodenal ulcer nighttime pain severity (76% vs 65%; p = 0.044), and improvement in overall well-being (55% vs 41%; p = 0.009). At wk 4, the proportion of patients with normalization of overall well-being was significantly higher in the rabeprazole group than in the ranitidine group (45% vs 29%; p = 0.003). Rabeprazole was safe and well tolerated in this study. CONCLUSIONS: In patients with active duodenal ulcer disease, rabeprazole 20 mg q.a.m. is superior to ranitidine 150 mg b.i.d. in healing, resolving ulcer pain frequency, improving nighttime pain severity, and improving overall well-being. Rabeprazole is an effective and well-tolerated alternative treatment for patients with active duodenal ulcer disease.

Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group.

CONTEXT: Previous studies have shown oseltamivir, a neuraminidase inhibitor, to be effective in preventing influenza and treating experimental influenza. OBJECTIVE: To evaluate the efficacy and safety of oseltamivir in the treatment of naturally acquired influenza infection. DESIGN: Randomized, placebo-controlled, double-blind study conducted January through March 1998. SETTING: Sixty primary care and university health centers throughout the United States. PARTICIPANTS: A total of 629 healthy nonimmunized adults aged 18 to 65 years with febrile respiratory illness of no more than 36 hours' duration with temperature of 38 degrees C or more plus at least 1 respiratory symptom and 1 constitutional symptom. INTERVENTIONS: Individuals were randomized to 1 of 3 treatment groups with identical appearing pills: oral oseltamivir phosphate, 75 mg twice daily (n = 211) or 150 mg (n = 209) twice daily, or placebo (n = 209). MAIN OUTCOME MEASURES: Duration and severity of illness in individuals infected with influenza. RESULTS: Two individuals withdrew before receiving medication and were excluded from further analyses. A total of 374 individuals (59.6%) were infected with influenza. Their duration of illness was reduced by more than 30% with both oseltamivir, 75 mg twice daily (median, 71.5 hours; P < .001), and oseltamivir, 150 mg twice daily (median, 69.9 hours; P = .006), compared with placebo (median, 103.3 hours). Severity of illness was reduced by 38% (median score, 597 score-hours; P < .001) with oseltamivir, 75 mg twice daily, and by 35% (median score, 626 score-hours; P < .001) with oseltamivir, 150 mg twice daily, vs placebo (median score, 963 score-hours). Oseltamivir treatment reduced the duration of fever and oseltamivir recipients returned to usual activities 2 to 3 days earlier than placebo recipients (P < or = .05). Secondary complications such as bronchitis and sinusitis occurred in 15% of placebo recipients compared with 7% of combined oseltamivir recipients (P = .03). Among all 629 subjects, oseltamivir reduced illness duration (76.3 hours and 74.3 hours for 75 mg and 150 mg, respectively, vs 97.0 hours for placebo; P = .004 for both comparisons) and illness severity (686 score-hours and 629 score-hours for 75 mg and 150 mg, respectively, vs 887 score-hours for placebo; P < .001 for both comparisons). Nausea and vomiting occurred more frequently in both oseltamivir groups (combined, 18.0% and 14.1%, respectively; P = .002) than in the placebo group (7.4% and 3.4%; P < .001). CONCLUSIONS: Our data suggest that oral oseltamivir treatment reduces the duration and severity of acute influenza in healthy adults and may decrease the incidence of secondary complications.

The ChemTrak Hp Chek fingerstick whole blood serology test for the detection of Helicobacter pylori infection.

OBJECTIVE: To evaluate a new whole blood serology test (Hp Chek; ChemTrak) that detects IgG antibodies to Helicobacter pylori. METHODS: The study was conducted at 10 sites within the United States. Patients undergoing upper endoscopy for dyspepsia were recruited for enrollment. Those treated for H. pylori infection within a year of endoscopy and those who had regularly used proton pump inhibitors, bismuth compounds, or antibiotics within a month of endoscopy were not eligible. During endoscopy, specimens were obtained from the corpus and antrum for histological examination, which was performed by a single experienced pathologist. The Hp Chek was tested using whole blood and serum. Serum was also tested with a reference enzyme-linked immunosorbent assay (ELISA) at a centralized location. Test characteristics for the Hp Chek and ELISA were calculated using histology as the "gold standard." RESULTS: Two hundred eighty-seven patients (140 women and 147 men; mean age 53 +/- 6 yr) were enrolled. The Hp Chek was easy to perform and yielded results 9 min after inoculation of the test cassette with whole blood or serum. When the Hp Chek used with whole blood was compared with histology as the gold standard, the sensitivity was 88%, specificity 85%, positive predictive value 83%, negative predictive value 90%, and percent agreement 86%. There were no statistically significant differences among the results obtained with the Hp Chek using whole blood, the Hp Chek using serum, or reference ELISA. CONCLUSIONS: The Hp Chek whole blood serology test was easy to perform and rapid and yielded performance characteristics comparable to those of a reference ELISA or the Hp Chek used with serum.

Laparoscopic repair of a colonoscopic perforation.

We report a case of laparoscopic repair of a diagnostic colonoscopic perforation. No other such reports were noted in the literature. The management of colonoscopic perforations has become controversial. Operative vs nonoperative treatment is continually debated. The morbidity of operative management is significant. Colostomy is often performed. Laparoscopy should allow early evaluation of operative patients and primary repair of those with minimal contamination and no residual pathology. The benefits of minimally invasive surgery, such as shortened hospitalization and rapid return to full activities, including work, were realized in our patient. Laparoscopy should be considered in the selective management of colonoscopic perforations.

Triple therapy with lansoprazole, clarithromycin, and amoxicillin for the cure of Helicobacter pylori infection: a short report.

BACKGROUND: Given the therapeutic potential of proton pump inhibitor-based triple therapy for successful cure of Helicobacter pylori infection, we evaluated the efficacy and safety of lansoprazole with clarithromycin and amoxicillin in an open-label, single-center study. MATERIALS AND METHODS: H. pylori-positive patients self-administered lansoprazole, 30 mg; clarithromycin, 500 mg; and amoxicillin, 1 gm bid for 14 days. Patients were assessed pretreatment, at which time the presence of H. pylori was documented by rapid urease test, culture, or histology, following study drug administration (week 2) for a brief evaluation only, and at least 4 weeks posttreatment (week 6), which included endoscopy with collection of biopsy specimens for culture and histology testing. RESULTS: Primary clarithromycin and metronidazole resistance were observed in 6% (2 of 30) and 43% (13 of 30) of study patients, respectively. One month after the end of therapy, H. pylori infection was cured in 23 of 25 patients (92%; 95% confidence interval, 74%-99%). The triple-therapy regimen was well-tolerated; 17% of patients (5 of 30) reported mild to moderate adverse effects during the treatment period. CONCLUSION: A 2-week, triple-drug combination of lansoprazole, clarithoromycin, and amoxicillin is highly effective for cure of H. pylori infection. Additionally, the triple-drug combination was well-tolerated by patients infected with H. pylori.