Effects of preceding endoscopic mucosal resection on the efficacy and safety of radiofrequency ablation for treatment of Barrett's esophagus: results from the United States Radiofrequency Ablation Registry.

The effects of preceding endoscopic mucosal resection (EMR) on the efficacy and safety of radiofrequency ablation (RFA) for treatment of nodular Barrett's esophagus (BE) is poorly understood. Prior studies have been limited to case series from individual tertiary care centers. We report the results of a large, multicenter registry. We assessed the effects of preceding EMR on the efficacy and safety of RFA for nodular BE with advanced neoplasia (high-grade dysplasia or intramucosal carcinoma) using the US RFA Registry, a nationwide study of BE patients treated with RFA at 148 institutions. Safety outcomes included stricture, gastrointestinal bleeding, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), and number of RFA treatments needed to achieve CEIM. Analyses comparing patients with EMR before RFA to patients undergoing RFA alone were performed with Student's t-test, Chi-square test, logistic regression, and Kaplan-Meier analysis. Four hundred six patients were treated with EMR before RFA for nodular BE, and 857 patients were treated with RFA only for non-nodular BE. The total complication rates were 8.4% in the EMR-before-RFA group and 7.2% in the RFA-only group (P = 0.48). Rates of stricture, bleeding, and hospitalization were not significantly different between patients treated with EMR before RFA and patients treated with RFA alone. CEIM was achieved in 84% of patients treated with EMR before RFA, and 84% of patients treated with RFA only (P = 0.96). CED was achieved in 94% and 92% of patients in EMR-before-RFA and RFA-only group, respectively (P = 0.17). Durability of eradication did not differ between the groups. EMR-before-RFA for nodular BE with advanced neoplasia is effective and safe. The preceding EMR neither diminished the efficacy nor increased complication rate of RFA treatment compared to patients with advanced neoplasia who had RFA with no preceding EMR. Preceding EMR is not associated with poorer outcomes in RFA.

Mesalazine granules 1.5 g once-daily maintain remission in patients with ulcerative colitis who switch from other 5-ASA formulations: a pooled analysis from two randomised controlled trials.

BACKGROUND: Mesalazine (mesalamine) granules (MG) were shown to be effective for the maintenance of remission of ulcerative colitis (UC) in two double-blind placebo-controlled trials. AIM: To evaluate the efficacy of once-daily MG for maintenance of remission in patients with UC who switched from other 5-aminosalicylic acid (5-ASA) formulations. METHODS: Data from two independent multicenter, randomised, double-blind, placebo-controlled, 6-month trials evaluating patients with UC in remission were combined for analysis of a subpopulation of patients who switched from other 5-ASA formulations to MG 1.5 g or placebo upon randomisation. The primary endpoint was the percentage of patients who remained relapse-free at Month 6 or end of treatment. Relapse was defined as a Sutherland Disease Activity Index (SDAI) rectal bleeding score ≥1 and mucosal appearance score ≥2, a UC flare or medication used to treat a UC flare. RESULTS: Of the 487 patients who received 5-ASA maintenance therapy at enrolment, 322 were in the MG group and 165 were in the placebo group. The percentage of patients who remained relapse-free (based on Sutherland Disease Activity Index scores) after 6 months was significantly higher with MG than placebo (78.3% vs. 58.8%, P < 0.001). Rectal bleeding, stool frequency and the physician's rating of disease activity remained unchanged after 6 months in a higher percentage of patients using MG compared with those on placebo (P < 0.004 for each endpoint). CONCLUSION: Mesalazine granules 1.5 g once-daily is effective for maintenance of remission in UC patients who switch from other 5-ASA formulations. ClinicalTrials.gov identifiers NCT00744016, NCT00767728.

Clinical trial: once-daily mesalamine granules for maintenance of remission of ulcerative colitis - a 6-month placebo-controlled trial.

BACKGROUND: Ulcerative colitis (UC) is a chronic relapsing and remitting idiopathic inflammatory bowel disorder. AIM: To evaluate once-daily mesalamine (mesalazine) granules (MG) for maintenance of remission of UC. METHODS: Randomized, double-blind, placebo-controlled trial of patients (n=209 MG, n=96 placebo) with UC in remission [revised Sutherland Disease Activity Index (SDAI) rectal bleeding=0, mucosal appearance <2] who took MG 1.5 g or placebo once-daily for up to 6 months. Primary efficacy endpoint: the percentage of patients who remained relapse-free at month 6/end of treatment. Relapse was defined as SDAI rectal bleeding score ≥1 and a mucosal appearance score ≥2, a UC flare, or initiation of medication to treat a UC flare. RESULTS: The percentage of relapse-free patients at month 6/end of treatment was higher with MG than placebo (78.9% vs. 58.3%, P < 0.001) in the intent-to-treat analysis. Significant differences (P ≤ 0.025) favouring MG were observed for most secondary endpoints including improvement in rectal bleeding, physician's disease activity rating, stool frequency, the SDAI at month 6/end of treatment, patients classified as a treatment success and relapse-free duration. The incidence of adverse events was similar between groups. CONCLUSIONS: Once-daily mesalamine (mesalazine) was effective in maintaining remission of UC for 6 months.

Radiofrequency ablation of Barrett's esophagus: outcomes of 429 patients from a multicenter community practice registry.

BACKGROUND AND STUDY AIMS: The use of radiofrequency ablation (RFA) for complete eradication of Barrett's esophagus has shown promise in trials conducted at predominantly tertiary academic centers; however less is known regarding outcomes in the community. We evaluated the safety and efficacy of RFA for Barrett's esophagus delivered in a community practice setting. PATIENTS AND METHODS: This was a multicenter registry conducted in community-based gastroenterology practices. Patients had confirmed intestinal metaplasia with or without dysplasia on biopsy of a Barrett's esophagus. Intervention was step-wise RFA with follow-up esophageal biopsies. Endpoints were histology-based; complete response was defined as all biopsies at most recent endoscopy negative for intestinal metaplasia (CR-IM) or dysplasia (CR-D). Three cohorts were reported: 1) safety cohort, all patients; 2) efficacy cohort A, patients with at least one biopsy session after initial treatment; 3) efficacy cohort B, patients with at least one biopsy session > or = 1 year after initial treatment. RESULTS: The safety cohort included 429 patients (71 % men, median age 59 years, median Barrett's segment 3.0 cm). There were no serious adverse events (bleeding, perforation, death), and a stricture occurred after 1.1 % of cases (2.1 % of patients). In efficacy cohort A (n = 338), CR-IM and CR-D were achieved in 72 % and 89 % of patients, respectively (median follow-up 9 months). In efficacy cohort B (n = 137), CR-IM and CR-D were achieved in 77 % and 100 % of patients, respectively (median follow-up 20 months). CONCLUSIONS: In this multicenter registry conducted at four community-based practices, the observed safety and efficacy outcomes associated with RFA for Barrett's esophagus are comparable to those previously reported in multicenter trials from predominantly tertiary academic centers.

Long-term safety of tegaserod in patients with constipation-predominant irritable bowel syndrome.

BACKGROUND: Tegaserod is a 5-hydroxytryptamine-4 receptor partial agonist. Oral administration causes gastrointestinal effects resulting in increased gastrointestinal motility and attenuation of visceral sensation. AIM: : To determine the long-term safety and tolerability of tegaserod in patients suffering from irritable bowel syndrome with constipation as the predominant symptom of altered bowel habits. METHOD: A multicentre, open-label study with flexible dose titration of tegaserod in out-patients suffering from constipation-predominant irritable bowel syndrome. RESULTS: A total of 579 patients with constipation-predominant irritable bowel syndrome were treated with tegaserod. Of these, 304 (53%) completed the trial. The most common adverse events, classified as related to tegaserod for any dose, were mild and transient diarrhoea (10.1%), headache (8.3%), abdominal pain (7.4%) and flatulence (5.5%). Forty serious adverse events were reported in 25 patients (4.4% of patients) leading to discontinuation in six patients. There was one serious adverse event, acute abdominal pain, classified as possibly related to tegaserod. There were no consistent differences in adverse events between patients previously exposed to tegaserod and those treated de novo. No pattern-forming tegaserod-related abnormalities in haematological and biochemical laboratory tests, urinalysis, blood pressure, pulse rate or electrocardiograms were found. CONCLUSIONS: Tegaserod appears to be well tolerated in the treatment of patients with constipation-predominant irritable bowel syndrome. The adverse event profile, clinical laboratory evaluations, vital signs and electrocardiogram recordings revealed no evidence of any unexpected adverse events, and suggest that treatment is safe over a 12-month period.

Planning strategies for the avoidance of pitfalls in intervention research.

BACKGROUND: With the exception of large clinical trials, few studies in nursing and other social sciences test interventions. The discipline of nursing needs to maintain a full range of research designs for continued knowledge development. Intervention research presents unique opportunities and challenges for the novice as well as the seasoned researcher. Some of these methodological challenges include the complex nature of human subjects and interventions, including many factors that interfere with the study variables. Preliminary studies often reveal challenges that may not always be predicted or reflected in research texts. These challenges may be as important as the study results for success in future research efforts. PURPOSE: Difficulties encountered in intervention research and suggested strategies for maintaining the integrity of the study are addressed. These challenges include maintaining an adequate sample size, intervention demands, measuring variables, timing issues, and experiencing unexpected events. FINDINGS AND CONCLUSIONS: Strategies presented include the importance of extensive planning, minimizing subject expectations and rewarding efforts, attention to control group members, incorporating retention strategies, expanding knowledge of variables and the study population, preliminary studies as well as anticipating unexpected events. The need for enhanced communication among nurse researchers, educators and clinicians is addressed. In the current health care arena, nurse researchers must understand organizational dynamics and marketing strategies. Collaborative research efforts can increase the visibility of nursing research as well as funding opportunities.

FIDDLEHEAD, a gene required to suppress epidermal cell interactions in Arabidopsis, encodes a putative lipid biosynthetic enzyme.

In plants, the outer epidermal cell wall and cuticle presents a semipermeable barrier that maintains the external integrity of the plant and regulates the passage of various classes of molecules into and out of the organism. During vegetative development, the epidermal cells remain relatively inert, failing to respond to wounding or grafting. During reproductive development and fertilization, however, the epidermis is developmentally more labile and participates in two types of contact-mediated cell interactions: organ fusion and pollen hydration. Here we describe the isolation and characterization of one gene whose product normally functions in blocking both types of epidermal cell interactions during vegetative development: the FIDDLEHEAD gene. As suggested by previous biochemical analyses, the gene encodes a protein that is probably involved in the synthesis of long-chain lipids found in the cuticle and shows similarity to a large class of genes encoding proteins related to beta-ketoacyl-CoA synthases and chalcone synthases. In situ hybridization reveals an epidermal pattern of expression consistent with a role for this protein in the synthesis of lipid components that are thought to localize extracellularly and probably modify the properties of the cuticle.

Complex sexual signals for the male gametophyte.

The pollen grain and the pollen tube that grows from it are complex entities which must respond to a diverse array of signals to carry out their roles in sexual reproduction. Research is beginning to reveal the nature both of the signals and of the signal transduction machinery that converts these signals into directional, polarized growth.

Behavioral, nutritional, and toxicological responses of cattle to ensiled leafy spurge.

Yearling cattle (n = 25; 416.1 +/- 25.9 kg) were stratified by weight and gender across five groups. Group 1 (OAT) was offered oat/rape haylage (ORH) for ad libitum consumption during two daily feeding periods. Group 2 (SPURGE) was offered leafy spurge/grass haylage (LSGH) for ad libitum consumption during the same feeding periods. Group 3 was offered ORH in an amount equal to the average amount of LSGH consumed by SPURGE at the previous feeding. Group 4 (MIX) was offered LSGH mixed with ORH for ad libitum consumption during the two feeding periods. Group 5 (PAIR) received the equivalent amount of ORH consumed by MIX at the previous feeding. The DMI for OAT, SPURGE, and MIX were similar at the first feeding (P = .52). The SPURGE group consumed very little LSGH thereafter and was removed from the trial. The OAT and MIX groups consumed similar amounts of DM daily on d 1 to 4 when the ration offered to MIX was only 7% LSGH (P = .33). When LSGH made up > or = 21% of the mixture (d 7 to 32), the OAT group consumed more daily DM than did MIX (P < .05). The spurge/oatlage ration offered to MIX was less digestible than the oatlage-only ration offered to PAIR (P < or = .01). Even though blood chemistry did not indicate that LSGH consumption caused organ damage, its intake caused minor alterations (P < or = .05) in serum albumin, calcium, gamma glutamyltransferase, P, K, and urea nitrogen. No gross or microscopic lesions, infectious agents, or significant numbers of parasites were detected in any of the carcasses or tissues examined. The MIX group had diarrhea for much of the trial. In Trial 2, five yearling cattle were adapted to a mixture of 21% LSGH and 79% ORH. Then they were simultaneously offered three mixtures of spurge and oat haylages: 1) spurge ensiled with a microbial inoculant (LSGH); 2) spurge ensiled with the same inoculant and a cellulolytic/hemicellulolytic enzyme (ENZ); and 3) spurge ensiled with the same inoculant and molasses (MOL). The mixture with ENZ was preferred over those with MOL or LSGH (P < .001), but the amounts consumed were low and similar to those for LSGH-ORH in Trial 1 when amounts of ENZ and LSGH in the mixtures were similar. The ENZ mixture may have been more palatable than LSGH and MOL because it had less (P < .05) lactic acid, but intake of ENZ indicates that it had aversive characteristics, like LSGH. Ensiling leafy spurge did little, if anything, to improve its palatability to cattle.

Initial experience with fenoldopam in children.

Fenoldopam is a direct-acting vasodilator that acts at the postsynaptic dopamine 1 receptors in renal, coronary, cerebral, and splanchnic vasculature resulting in arterial dilation and a lowering of the mean arterial pressure (MAP). Preliminary evidence suggests its efficacy in the treatment of hypertensive urgencies and emergencies in adults. We present four children in whom fenoldopam was used to control MAP in various clinical scenarios, including hypertensive emergencies and urgencies, intraoperative reduction of MAP for controlled hypotension, and control of MAP during extracorporeal membrane oxygenation. The possible applications of fenoldopam and suggested dosing regimens in children are reviewed.

Routine use of ultrasound during pregnancy.

Ultrasound technology offers valuable information when used as a diagnostic tool during a pregnancy at risk for complications. Its use has expanded greatly to uncomplicated pregnancies as a result of expectant parents' desire to see their baby or to know its gender. Many women are having ultrasounds without being given factual information regarding the purposes, risks, and/or benefits of this procedure. Decisions regarding ultrasound sonography could have a significant physical or emotional impact on the pregnancy, and informed decision making can take place only when the patient is properly educated. Issues regarding ultrasound benefits, safety, controversies, and information helpful to nurse practitioners involved in sonography are addressed in this article.

Budesonide enema for the treatment of active, distal ulcerative colitis and proctitis: a dose-ranging study. U.S. Budesonide enema study group.

BACKGROUND & AIMS: Budesonide is a highly potent topical glucocorticosteroid that is characterized by low systemic availability as a result of high first-pass hepatic metabolism. The aim of this study was to evaluate the efficacy and safety of three doses of an enema preparation of budesonide in patients with active distal ulcerative colitis/proctitis. METHODS: In a double-blind multicenter trial, 233 patients were randomized to receive either a placebo enema or budesonide enema at a dose of 0.5 mg/100 mL, 2.0 mg/100 mL, or 8.0 mg/100 mL. The primary efficacy variables were an improvement of sigmoidoscopic inflammation grade, total histopathology score, and remission rates. Effects on cortisol concentrations were also assessed. RESULTS: After 6 weeks of treatment, there was significant improvement in sigmoidoscopy and histopathology scores in the budesonide 2.0-mg and 8.0-mg dose groups compared with placebo. Remission was achieved in 19% of patients in the 2.0-mg budesonide group (P

Genetic analysis of organ fusion in Arabidopsis thaliana.

Postgenital organ fusion occurs most commonly during reproductive development and is important in many angiosperms during genesis of the carpel. Although a number of mutants have been described that manifest ectopic organ fusion, little is known about the genes involved in regulating this process. In this article we describe the characterization of a collection of 29 Arabidopsis mutants showing an organ fusion phenotype. Mapping and complementation analyses revealed that the mutant alleles define nine different loci distributed throughout the Arabidopsis genome. Multiple alleles were isolated for the four complementation groups showing the strongest organ fusion phenotype while the remaining five complementation groups, all of which show only weak floral organ fusion, have a single representative allele. In addition to fusion events between aerial parts of the shoot, some mutants also show abnormal ovule morphology with adjacent ovules joined together at maturity. Many of the fusion mutants isolated have detectable differences in the rate at which chlorophyll can be extracted; however, in one case no difference could be detected between mutant and wild-type plants. In three mutant lines pollen remained unresponsive to contact with the mutant epidermis, demonstrating that organ fusion and pollen growth responses can be genetically separated from one another.

Nonperinatal nosocomial transmission of Candida albicans in a neonatal intensive care unit: prospective study.

Nosocomial Candida albicans infections have become a major cause of morbidity and mortality in neonates in neonatal intensive care units (NICUs). To determine the possible modes of acquisition of C. albicans in hospitalized neonates, we conducted a prospective study at Grady Memorial Hospital, Atlanta, Ga. Clinical samples for fungal surveillance cultures were obtained at birth from infants (mouth, umbilicus, and groin) and their mothers (mouth and vagina) and were obtained from infants weekly until they were discharged. All infants were culture negative for C. albicans at birth. Six infants acquired C. albicans during their NICU stay. Thirty-four (53%) of 64 mothers were C. albicans positive (positive at the mouth, n = 26; positive at the vagina, n = 18; positive at both sites, n = 10) at the time of the infant's delivery. A total of 49 C. albicans isolates were analyzed by restriction endonuclease analysis and restriction fragment length polymorphism analysis by using genomic blots hybridized with the CARE-2 probe. Of the mothers positive for C. albicans, 3 of 10 were colonized with identical strains at two different body sites, whereas 7 of 10 harbored nonidentical strains at the two different body sites. Four of six infants who acquired C. albicans colonization in the NICU had C. albicans-positive mothers; specimens from all mother-infant pairs had different restriction endonuclease and CARE-2 hybridization profiles. One C. albicans-colonized infant developed candidemia; the colonizing and infecting strains had identical banding patterns. Our study indicates that nonperinatal nosocomial transmission of C. albicans is the predominant mode of acquisition by neonates in NICUs at this hospital; mothers may be colonized with multiple strains of C. albicans simultaneously; colonizing C. albicans strains can cause invasive disease in neonates; and molecular biology-based techniques are necessary to determine the epidemiologic relatedness of maternal and infant C. albicans isolates and to facilitate determination of the mode of transmission.

Evaluation of wheat middlings as a supplement for beef cows grazing native winter range with differing forage availabilities.

We conducted two studies to compare wheat middlings as a low-protein, highly digestible fiber supplement to soybean meal and corn-soybean meal supplement for cows grazing winter range. In two 60-d winter grazing trials (December to February) cows (BW 500 kg) were allotted by age and weight to a 2 x 4 factorial with two forage availabilities and four supplements. Cows received either soybean meal (SBM), corn-soybean meal (CS), low wheat middlings (LWM), or high wheat middlings (HWM). The SBM and LWM supplements were formulated to provide the same daily CP, and CS and HWM provided the same daily CP and ME. In a 4 x 4 Latin square, four ruminally fistulated steers (BW 765 kg) received the same supplements and had free access to mature prairie hay. Cows grazing the high forage pasture gained more (P < .01) weight than cows grazing the low forage pasture. Cows supplemented with HWM gained less weight (P = .05) than cows supplemented with a similar amount of CP and ME from CS. Weight change of cows receiving SBM or LWM was similar. Increasing the amount of wheat middlings from LWM to HWM increased weight change (P = .04). In Exp. 2, SBM and LWM had similar total digestible DMI (DDMI). Steers supplemented with CS had higher total (P = .08) DDMI than HWM. Supplementation with HWM resulted in lower total (P = .02) DDMI than LWM. Response to SBM and LWM was similar. The CS and HWM resulted in beneficial performance responses as well as increasing the level of wheat middlings from low to high.

Developmental regulation of cell interactions in the Arabidopsis fiddlehead-1 mutant: a role for the epidermal cell wall and cuticle.

Although the plant epidermis serves primarily a protective role, during plant development some epidermal cells specialize, becoming competent to interact not only with pollen but also with other epidermal cells. In the former case, these interactions mediate recognition, germination, and pollen growth responses and, in the latter case, result in interorgan fusions which, most commonly, alter floral architecture in ways that are thought to promote reproductive success. In either case, all of the initial signaling events must take place across the cell wall and cuticle. In Arabidopsis, mutation of the FIDDLEHEAD gene alters the shoot epidermis such that all epidermal cells become competent to participate in both types of interactions. In fdh-1 mutants, epidermal cells manifest not only a contact-mediated fusion response but also interact with pollen. Since carpel epidermal derivatives manifest both of these properties, we postulated that fdh-1 epidermal cells were ectopically expressing a carpel-like program. In this report we demonstrate that manifestation of the fdh-1 phenotype does not require the product of the AGAMOUS gene, indicating that the phenotype is either independent of the carpel development program or that fdh-1 mutations activate a carpel-specific developmental program downstream of the AG gene. Furthermore, we demonstrate that plants bearing mutations in the fdh-1 gene show significant changes in cell wall and cuticular permeability. Biochemical analyses of the lipid composition of the crude cell wall fraction reveal that fdh-1 cell walls differ from wild-type and manifest significant changes in high-molecular-weight lipid peaks. These results suggest that cell wall and cuticular permeability may be important determinants in developmental signaling between interacting cells and implicate lipids as important factors in modulating the selectivity of the permeability barrier presented by the epidermal cell wall and cuticle.

Effectiveness of cholecystokinin-stimulated cholescintigraphy in the diagnosis and treatment of acalculous gallbladder disease.

We retrospectively reviewed the medical records of 107 patients in two community hospitals who had undergone cholecystokinin-stimulated cholescintigraphy with ejection fraction to determine whether this test is reliable in identifying patients whose symptoms will improve following cholecystectomy. Patients with cholelithiasis or incomplete medical records and patients who could not be interviewed were excluded from the study. Forty-two of 58 study patients (72%) had an abnormal ejection fraction (defined as 35% or less); 27 of 42 patients (64%) underwent cholecystectomy. Twenty-six of 27 (96%) reported lessening of or resolution of symptoms following cholecystectomy. Sixty-seven per cent of the surgical specimens from the 27 patients demonstrated chronic cholecystitis. Fifteen of 42 patients (36%) with abnormal ejection fractions did not undergo cholecystectomy; 12 of 15 (80%) also reported lessening or resolution of symptoms. Of the 16 of 58 patients with a normal ejection fraction, 2 underwent cholecystectomy and reported resolution of symptoms. Five of 14 (36%) with normal ejection fractions who did not undergo cholecystectomy reported improvement. In this series, most patients with an abnormal ejection fraction had lessening of symptoms regardless of whether they underwent cholecystectomy.

Animal exposure risks. Implications for occupational health nurses.

1. Diseases transmitted from animals to humans, referred to as zoonoses, pose risks for persons occupationally exposed to animals. 2. Occupational health nurses should be proactive in identifying potential occupational health risks and educating employees to protect themselves from animal exposure risks. 3. Exposure history should include exposure to birds and animals during occupational and recreational activities. 4. Primary prevention is critical, as immunizations and treatments are limited and include many associated risks.