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The novel use of peroral endoscopic myotomy (POEM) in the treatment of Zenker's diverticulum (ZD) was recently described in case reports. The aim of this study is to report a multicenter experience with the POEM technique in the management of ZD. This is a multicenter international retrospective study involving 10 centers. The Zenker's POEM technique was performed using principles of submucosal endoscopy. Seventy-five patients (73.3 ± 1.2 years, 33 women) were included with a mean Charleson comorbidity index of 4 ±.2. The mean size of ZD was 31.3 ± 1.6 mm (range, 10-89). The overall technical success rate was 97.3% (73/75). There were 2 technical failures because of the inability to locate the septum and failed tunnel creation. Adverse events occurred in 6.7% (5/75): 1 bleed (mild) conservatively managed and 4 perforations (1 severe, 3 moderate). The mean procedure time was 52.4 ± 2.9 minutes, and mean length of hospital stay was 1.8 ±.2 days. Clinical success was achieved in 92% (69/75) with a decrease in mean dysphagia score from 1.96 to.25 (P <.0001). The median length of follow-up was 291.5 days (interquartile range, 103.5-436). At the 12-month follow-up, 1 patient reported symptom recurrence. Endoscopic management of ZD using the POEM technique is novel and feasible with promising efficacy and safety results. Long-term follow-up is needed to ensure durability of response. In addition, comparative studies with other treatment modalities are warranted. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product. [ABSTRACT FROM AUTHOR]

The pharmacokinetic behavior of naturally occurring isoflavones has been determined for the first time in healthy adults. We compared plasma kinetics of pure daidzein, genistein and their beta-glycosides administered as a single-bolus dose to 19 healthy women. This study demonstrates differences in the pharmacokinetics of isoflavone glycosides compared with their respective beta-glycosides. Although all isoflavones are efficiently absorbed from the intestinal tract, there are striking differences in the fate of aglycones and beta-glycosides. Mean time to attain peak plasma concentrations (t(max)) for the aglycones genistein and daidzein was 5.2 and 6.6 h, respectively, whereas for the corresponding beta-glycosides, the t(max) was delayed to 9.3 and 9.0 h, respectively, consistent with the residence time needed for hydrolytic cleavage of the glycoside moiety for bioavailability. The apparent volume of distribution of isoflavones confirms extensive tissue distribution after absorption. Plasma genistein concentrations are consistently higher than daidzein when equal amounts of the two isoflavones are administered, and this is accounted for by the more extensive distribution of daidzein (236 L) compared with genistein (161 L). The systemic bioavailability of genistein [mean AUC = 4.54 microg/(mL x h)] is much greater than that of daidzein [mean AUC = 2.94 microg/(mL x h)], and bioavailability of these isoflavones is greater when ingested as beta-glycosides rather than aglycones as measured from the area under the curve of the plasma appearance and disappearance concentrations. The pharmacokinetics of methoxylated isoflavones show distinct differences depending on the position of the methoxyl group in the molecule. Glycitin, found in two phytoestrogen supplements, underwent hydrolysis of the beta-glycoside moiety and little further biotransformation, leading to high plasma glycitein concentrations. Biochanin A and formononetin, two isoflavones found in one phytoestrogen supplement, were rapidly and efficiently demethylated, resulting in high plasma genistein and daidzein concentrations typically observed after the ingestion of soy-containing foods. These differences in pharmacokinetics and metabolism have implications for clinical studies because it cannot be assumed that all isoflavones are comparable in their pharmacokinetics and bioavailability. An analysis of 33 phytoestrogen supplements and extracts revealed considerable differences in the isoflavone content from that claimed by the manufacturers. Plasma concentrations of isoflavones show marked qualitative and quantitative differences depending on the type of supplement ingested. These studies indicate a need for improvement in quality assurance and standardization of such products. [ABSTRACT FROM AUTHOR]

Background & Aims In patients with persistent symptoms after Heller myotomy (HM), treatment options include repeat HM, pneumatic dilation, or peroral endoscopic myotomy (POEM). We evaluated the efficacy and safety of POEM in patients with achalasia with prior HM vs without prior HM. Methods We conducted a retrospective cohort study of 180 patients with achalasia who underwent POEM at 13 tertiary centers worldwide, from December 2009 through September 2015. Patients were divided into 2 groups: those with prior HM (HM group, exposure; n = 90) and those without prior HM (non-HM group; n = 90). Clinical response was defined by a decrease in Eckardt scores to 3 or less. Adverse events were graded according to criteria set by the American Society for Gastrointestinal Endoscopy. Technical success, clinical success, and rates of adverse events were compared between groups. Patients were followed up for a median of 8.5 months. Results POEM was technically successful in 98% of patients in the HM group and in 100% of patients in the non-HM group ( P = .49). A significantly lower proportion of patients in the HM group had a clinical response to POEM (81%) than in the non-HM group (94%; P = .01). There were no significant differences in rates of adverse events between the groups (8% in the HM group vs 13% in the non-HM group; P = .23). Symptomatic reflux and reflux esophagitis after POEM were comparable between groups. Conclusions POEM is safe and effective for patients with achalasia who were not treated successfully by prior HM. Although the rate of clinical success in patients with prior HM is lower than in those without prior HM, the safety profile of POEM is comparable between groups. [ABSTRACT FROM AUTHOR]

Background and Aims Per-oral endoscopic myotomy (POEM) has shown promising safety and efficacy in short-term studies. However, long-term follow-up data are very limited. The aims of this study were to assess (1) clinical outcome of patients with a minimum post-POEM follow-up of 2 years and (2) factors associated with long-term clinical failure after POEM. Methods A retrospective chart review was performed that included all consecutive patients with achalasia who underwent POEM with a minimum follow-up of 2 years at 10 tertiary-care centers. Clinical response was defined by a decrease in Eckardt score to 3 or lower. Results A total of 205 patients (45.8% men; mean age, 49 years) were followed for a median of 31 months (interquartile range, 26-38 months). Of these, 81 patients (39.5%) had received previous treatment for achalasia before POEM. Clinical success was achieved in 98% (185/189), 98% (142/144), and 91% (187/205) of patients with follow-up within 6 months, at 12 months, and ≥24 months, respectively. Of 185 patients with clinical response at 6 months, 11 (6%) experienced recurrent symptoms at 2 years. History of previous pneumatic dilation was associated with long-term treatment failure (odds ratio, 3.41; 95% confidence interval, 1.25-9.23). Procedure-related adverse events occurred in 8.2% of patients and only 1 patient required surgical intervention. Abnormal esophageal acid exposure and reflux esophagitis were documented in 37.5% and 18% of patients, respectively. However, these rates are simply a reference number among a very selective group of patients. Conclusions POEM is safe and provides high initial clinical success and excellent long-term outcomes. Among patients with confirmed clinical response within 6 months, 6% had recurrent symptoms by 2 years. [ABSTRACT FROM AUTHOR]

Abstract: Up to thirty percent of cocaine addicted individuals may meet diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD). Methylphenidate (MPH) is a highly effective and commonly used treatment for ADHD but, like cocaine, is a cardiovascular and central nervous system stimulant with the potential to cause toxicity at high doses. The present study was undertaken to investigate the likelihood of a toxic reaction in individuals who use cocaine while concurrently taking MPH. Seven non-treatment seeking cocaine-dependent individuals completed this placebo-controlled, crossover study with two factors: Medication (placebo, 60 mg MPH, 90 mg MPH) and Infusion (saline, 20 mg cocaine, 40 mg cocaine). Physiological measures included vital signs, adverse events, and electrocardiogram. Subjective response was measured with visual analog scale (VAS) ratings of craving and drug effect. Cocaine pharmacokinetic parameters were calculated for each participant at each drug combination, using a non-compartmental model. MPH was well tolerated, did not have a clinically significant impact on cocaine''s physiological effects, and decreased some of the positive subjective effects of cocaine. MPH did not significantly alter the pharmacokinetics of cocaine. The study results suggest that MPH at the doses studied can likely be used safely in an outpatient setting with active cocaine users. [Copyright &y& Elsevier]