Healing rates for moderate and severe oesophagitis.
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Enzyme Inhibitors↗
Biomedical subjects
C Hwang
Publications and source records attributed to C Hwang.
Changes in bacterial community structure correlate with initial operating conditions of a field-scale denitrifying fluidized bed reactor.
High levels of nitrate are present in groundwater migrating from the former waste disposal ponds at the Y-12 National Security Complex in Oak Ridge, TN. A field-scale denitrifying fluidized bed reactor (FBR) was designed, constructed, and operated with ethanol as an electron donor for the removal of nitrate. After inoculation, biofilms developed on the granular activated carbon particles. Changes in the bacterial community of the FBR were evaluated with clone libraries (n = 500 partial sequences) of the small-subunit rRNA gene for samples taken over a 4-month start-up period. Early phases of start-up operation were characterized by a period of selection, followed by low diversity and predominance by Azoarcus-like sequences. Possible explanations were high pH and nutrient limitations. After amelioration of these conditions, diversification increased rapidly, with the appearance of Dechloromonas, Pseudomonas, and Hydrogenophaga sequences. Changes in NO3, SO4, and pH also likely contributed to shifts in community composition. The detection of sulfate-reducing-bacteria-like sequences closely related to Desulfovibrio and Desulfuromonas in the FBR have important implications for downstream applications at the field site.
Bacteria↗
Efficacy of esomeprazole 40 mg vs. lansoprazole 30 mg for healing moderate to severe erosive oesophagitis.
BACKGROUND: Secondary analyses from previous studies indicated that esomeprazole was more effective than lansoprazole and omeprazole in healing moderate or severe (Los Angeles grades C or D) erosive oesophagitis (EE). AIM: To compare prospectively healing rates with esomeprazole vs. lansoprazole in patients with moderate to severe EE. METHODS: In this multicentre, randomized, double-blind, parallel-group trial, adult patients with endoscopically confirmed moderate or severe EE received esomeprazole 40 mg (n = 498) or lansoprazole 30 mg (n = 501) once daily for up to 8 weeks. The primary end point was EE healing through week 8. Secondary assessments included investigator-assessed resolution of symptoms and safety and tolerability. RESULTS: Time to healing was significantly different (P = 0.007), favouring esomeprazole. Estimated healing rates at week 8 were 82.4% with esomeprazole 40 mg and 77.5% with lansoprazole 30 mg. Heartburn resolved at week 4 in 72% and 64% of patients who received esomeprazole and lansoprazole, respectively (P = 0.005). Control of other GERD symptoms was similar between treatments. Both treatments were well tolerated. CONCLUSIONS: With 8 weeks' treatment, esomeprazole 40 mg once daily heals moderate to severe EE faster and in more patients, and resolves heartburn in more patients after 4 weeks of treatment, than lansoprazole 30 mg once daily.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Spatial and temporal variability of necrophagous Diptera from urban to rural areas.
The spatio-temporal variability of necrophagous fly assemblages in a linear series of habitats from central London to the rural surroundings in the south-west was studied using bottle traps between June 2001 and September 2002. A total of 3,314 individuals in 20 dipteran families were identified from 127 sampling occasions. Calliphoridae accounted for 78.6% of all the dipteran specimens, with Calliphora vicina Robineau-Desvoidy, being the most abundant species (2,603 individuals, 46.9%). Using canonical correspondence analyses (CCA) on 72 fly taxa, six sampled sites and 36 environmental variables, three habitat types corresponding to three groups of flies were identified. These were an urban habitat characterized by C. vicina, Lucilia illustris (Meigen) and L. sericata (Meigen), a rural grassland habitat, characterized by L. caesar (Linnaeus) and a rural woodland habitat characterized by Calliphora vomitoria (Linnaeus), Phaonia subventa (Harris), Neuroctena anilis (Fallén) and Tephrochlamys flavipes (Zetterstedt). Intermediate species (L. ampullacea Villeneuve and P. pallida (Fabricius), located between the three habitats, were also found. Temporal abundance of the 10 most abundant species showed fluctuations between seasons, having low numbers of captured individuals during winter. Correspondence analysis showed clearly seasonal patterns at Box Hill site. The species-habitat associations suggest habitat differentiation between necrophagous guilds in this area and may be of ecological value.
Animals↗
Ablation of postinfarction ventricular tachycardia guided by isolated diastolic potentials.
Frequent recurrences of ventricular tachycardia (VT) despite implantable cardioverter-defibrillator (ICD) and antiarrhythmic drug therapy are a typical indication for catheter ablation. We performed endocardial mapping of an haemodynamically tolerated VT in a 67-year-old male patient. Isolated diastolic potentials (IDPs) of similar morphology were recorded during atrial paced rhythm at baseline and during monomorphic VT. The isolated potentials were required for initiation and maintenance of ventricular arrhythmia. These diastolic electrograms were considered to be part of the reentry circuit, as they remained constantly associated with VT during oscillations of cycle length and resetting. Validation of the ablation target was not performed by exact entrainment pacing in order to test the predictive value of the observed diagnostic phenomena. Radiofrequency (RF) energy applications were successful at the site where IDPs were recorded during atrial paced rhythm and VT. Ablation decreased the need for ICD therapies effectively in a patient with scar-related, slow VT.
Aged↗
Mxi1, a Myc antagonist, suppresses proliferation of DU145 human prostate cells.
BACKGROUND: Mxi1, an antagonist of c-Myc, maps to human chromosome 10q24-q25, a region altered in a substantial fraction of prostate tumors. Mice deficient for Mxi1 exhibit significant prostate hyperplasia. We studied the ability of Mxi1 to act as a growth suppressor in prostate tumor cells. METHODS: We infected DU145 prostate carcinoma cells with an Mxi1-expressing adenovirus (AdMxi1) in vitro, and measured Mxi1 expression, cell proliferation, soft agar colony formation, and cell cycle distribution. To explore mechanisms of Mxi1-induced growth arrest, we performed gene expression analysis. RESULTS: AdMxi1 infection resulted in reduced cell proliferation, reduced soft agar colony formation, and a higher proportion of cells in the G(2)/M phase of the cell cycle. This G(2)/M growth arrest was associated with elevated levels of cyclin B, and reduced levels of c-MYC and MDM2. CONCLUSIONS: The ability of AdMxi1 to suppress prostate tumor cell proliferation supports a role for Mxi1 loss in the pathogenesis of a subset of human prostate cancers. Prostate 47:194-204, 2001.
Adenoviridae↗
The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety.
BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. AIM: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. METHODS: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. RESULTS: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. CONCLUSIONS: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.
Administration, Oral↗
Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial.
OBJECTIVE: In patients with gastroesophageal reflux disease (GERD), esomeprazole, the S-isomer of omeprazole, has demonstrated pharmacological and clinical benefits beyond those seen with the racemic parent compound. This study was designed to further evaluate the efficacy and tolerability of esomeprazole relative to that of omeprazole in healing erosive esophagitis and resolving accompanying symptoms of GERD. METHODS: Esomeprazole 40 mg was compared with omeprazole 20 mg once daily in 2425 patients with erosive esophagitis (Helicobacter pylori negative by serology) in an 8-wk, multicenter, randomized, double-blind, parallel-group study conducted in 163 centers throughout the US. The primary efficacy endpoint was the proportion of patients with healed esophagitis at wk 8. Secondary endpoints were the proportion of patients healed at wk 4, resolution of heartburn at wk 4, time to first resolution and sustained resolution of heartburn, and proportion of heartburn-free days and nights. Safety and tolerability were also assessed. RESULTS: Significantly more patients were healed with esomeprazole versus omeprazole at wk 8 (93.7% vs 84.2%, p < 0.001; life table estimates, intention-to-treat analysis). Healing rates at wk 4 were 81.7% and 68.7%, respectively. Esomeprazole was superior to omeprazole for all secondary measures and had a similar safety profile. The most common adverse events in both treatment groups were headache, diarrhea, and nausea. CONCLUSIONS: Esomeprazole demonstrates significantly greater efficacy than omeprazole in the treatment of GERD patients with erosive esophagitis. The tolerability and safety of esomeprazole are comparable to that of omeprazole. (Am
Adult↗
Safety and efficacy of long term esomeprazole therapy in patients with healed erosive oesophagitis.
OBJECTIVE: To evaluate the safety and tolerability of long term treatment with esomeprazole in patients with healed erosive oesophagitis, and to describe its efficacy in the maintenance of healing. DESIGN AND SETTING: US multicentre, noncomparative, nonblind study. PATIENTS AND PARTICIPANTS: 807 patients with endoscopically confirmed healed erosive oesophagitis. METHODS: Patients received esomeprazole 40 mg once daily for up to 12 months. Adverse events and clinical laboratory tests were assessed over the study period. Endoscopy was performed at the final visit of the antecedent healing trials and at months 6 and 12 of the current safety trial; gastric biopsies were obtained at the initial visit of the healing trials and at the end of the safety trial. RESULTS: 80.9% of patients completed 6 months of treatment; 76.6% completed 12 months of treatment. There were no serious drug-related adverse events. Diarrhoea, abdominal pain, flatulence, and headache were the only treatment-related adverse events reported by >3% of patients. Mean changes in laboratory measures were generally small and not clinically meaningful. Plasma gastrin levels increased, as expected, and reached a plateau after 3 months. No changes in gastric histological scores were noted in the majority of patients. Evaluation of gastric biopsies revealed an overall decline in chronic inflammation and atrophy. Intestinal metaplasia findings remained essentially unchanged. Life table estimates of maintenance of healing were 93.7% [95% confidence interval (CI) 92.0 to 95.5%] at 6 months and 89.4% (95% CI 87.0 to 91.7%) at 12 months. CONCLUSIONS: Daily treatment with esomeprazole 40 mg for up to 1 year in patients with healed erosive oesophagitis was generally well tolerated and effective. No safety concerns arose.
Adolescent↗
Vein of marshall cannulation for the analysis of electrical activity in patients with focal atrial fibrillation.
BACKGROUND: Whether or not the muscle bundle within the ligament of Marshall (LOM) can serve as the origin of focal atrial fibrillation (AF) is unknown. METHODS AND RESULTS: A total of 28 consecutive patients with paroxysmal AF underwent balloon-occlusion coronary sinus angiograms to identify the vein of Marshall (VOM). Attempts were then made to advance a 1.5-French electrophysiological catheter into the VOM via the coronary sinus orifice. In 17 of the 28 patients (10 of 17 were men aged 38+/-15 years), cannulation was successful. Double potentials were registered in 8 of these 17 patients. The first potential corresponded with local left atrial activation. The second potential was shorter and narrower than the first. The sequence of activation in the second potential in the VOM was proximal to distal. In 6 patients with direct VOM recordings, we documented that the origin of AF was in the muscle bundle within the LOM. Radiofrequency catheter ablation aimed at the insertion site of the VOM successfully terminated AF in 4 of these 6 patients. CONCLUSIONS: (1) It is possible to cannulate and to record electrical potentials from the VOM. (2) The characteristics of the double potentials within the VOM suggest that the second potential is from the muscle bundle (Marshall bundle) within the LOM. (3) The Marshall bundle may be the origin of focal AF in some patients.
Adult↗
The ligament of Marshall: a structural analysis in human hearts with implications for atrial arrhythmias.
OBJECTIVES: We sought to study the anatomy of human ligament of Marshall (LOM). BACKGROUND: Although the LOM has been implicated in the genesis of focal atrial tachyarrhythmias, its gross anatomic and microscopic features in humans hearts have not been completely defined. METHODS: We studied seven postmortem human hearts from five men and two women with a mean age of 52 +/- 26 years. Four did not have any heart disease. One woman had dilated cardiomyopathy, and two men had chronic atrial fibrillation. A block of tissue encompassing the LOM from the coronary sinus (CS) cephalad, between the atrial appendage and left pulmonary veins, was dissected. Serial sections from this tissue were then stained with hematoxylin and eosin, trichrome, and/or tyrosine hydroxylase. RESULTS: The LOM consists of multiple sympathetic nerve fibers, ganglia, blood vessels and multiple myocardial tracts (Marshall Bundles) insulated by fibrofatty tissue. One or more myocardial tracts was inserted directly into the left atrial free wall and CS. The distance between insertion sites was 7.8 +/- 2.5 mm. Nerve fibers, some tyrosine hydroxylase positive, were present within the fibrofatty matrix and within the myocardial tracts. CONCLUSIONS: Human LOM 1) is innervated by sympathetic nerve fibers; 2) is more complex than the LOM in canine hearts; and 3) has multiple myocardial tract insertions into the left atrial free wall and CS, forming a substrate of reentry. Radiofrequency catheter ablation from the CS may fail to reach the free wall insertion.
Adult↗
Radiofrequency ablation of focal atrial tachycardia and atrioatrial conduction from recipient to donor after orthotopic heart transplantation.
After cardiac transplantation, atrial arrhythmias may develop in the residual recipient atrium and conduct to the donor heart. Radiofrequency (RF) ablation of the atrioatrial conduction may be effective in arrhythmia control, although the recipient atrium continues its tachycardia. We hypothesize that in patients with posttransplant atrial tachycardia, it is possible to ablate both the arrhythmogenic focus in the recipient atrium and the atrioatrial conduction. A 47-year-old patient who had orthotopic heart transplantation 9 months earlier underwent RF ablation procedure because of medically uncontrolled atrial arrhythmia. By conventional electrophysiologic mapping, we localized the focus of the atrial tachycardia in the recipient atrium and the electrical atrioatrial connection across the anastomotic suture line. Selective applications of RF energy eliminated both targets successfully. RF ablation of recipient atrial tachycardia and atrioatrial conduction from recipient to donor may lead to long-term success of arrhythmia control.
Catheter Ablation↗
Relation between ligament of Marshall and adrenergic atrial tachyarrhythmia.
BACKGROUND: The mechanism of the adrenergic atrial tachyarrhythmia is unclear. We hypothesize that the ligament of Marshall (LOM) is sensitive to adrenergic stimulation and may serve as a source of the adrenergic atrial tachyarrhythmia. METHODS AND RESULTS: We performed computerized mapping studies in isolated-perfused canine left atrial tissues from normal dogs (n=9) and from dogs with chronic atrial fibrillation (AF) induced by 10 to 41 weeks of rapid pacing (n=3). Before isoproterenol, spontaneous activity occurred in only one normal tissue (cycle length, CL >1300 ms). During isoproterenol infusion, automatic rhythm was induced in both normal tissues (CL=578+/-172 ms) and AF tissues (CL=255+/-29 ms, P<0.05). The origin of spontaneous activity was mapped to the LOM. In the AF tissues, but not the normal tissues, we observed the transition from rapid automatic activity to multiple wavelet AF. Ablation of the LOM terminated the spontaneous activity and prevented AF. Immunocytochemical studies of the LOM revealed muscle tracts surrounded by tyrosine hydroxylase-positive (sympathetic) nerves. CONCLUSIONS: We conclude that the LOM is richly innervated by sympathetic nerves and serves as a source of isoproterenol-sensitive focal automatic activity in normal canine atrium. The sensitivity to isoproterenol is upregulated after long-term rapid pacing and may contribute to the development of AF in this model.
Animals↗
Induction of tumor antigen-specific immunity in vivo by a novel vaccinia vector encoding safety-modified simian virus 40 T antigen.
BACKGROUND: Evidence that simian virus 40 (SV40) is associated with human mesotheliomas, osteosarcomas, and brain tumors suggests that a recombinant vaccine directed against lethal cancers expressing SV40 T antigen (Tag) could have clinical utility. To address this potential need, we designed a novel vaccinia virus construct that encodes an SV40 Tag in which oncogenic domains were excluded and immunogenic domains were preserved. We named this recombinant construct vaccinia-encoding safety-modified SV40 Tag (vac-mTag). METHODS: Purified vac-mTag was characterized by DNA sequencing, reverse transcription-coupled polymerase chain reaction, western blot analysis, and immunocytochemical techniques. Induction of Tag-specific immunity was examined by cytolytic T-cell assays, and the efficacy of vac-mTag in protecting animals against Tag-expressing tumors and in treating pre-established microscopic tumors was evaluated in vac-mTag-immunized BALB/c mice. RESULTS: The immune response elicited by vac-mTag in C57BL/6 and BALB/c mice included an SV40 Tag-specific cytolytic T-lymphocyte activity against syngeneic (identical genetic background) SV40 Tag-expressing tumor targets. Immunization of mice with a single dose of vac-mTag resulted in potent protection against subsequent challenge with a lethal mouse cancer expressing SV40 Tag. In addition, single-dose vac-mTag immunization coadministered with interleukin 2 produced a possible therapeutic effect against a preadministered microscopic (but lethal) burden of Tag-expressing tumor cells in vivo. CONCLUSION: vac-mTag induces an effective immune response in mice that is specific for a tumor-associated antigen. This response protects against a lethal tumor challenge and results in a possible therapeutic effect against Tag-expressing tumors in vivo. Thus, vac-mTag provides a new avenue for the development of therapies for human cancers thought to be associated with SV40.
Antineoplastic Agents↗
Recombinant vaccinia-PSA (PROSTVAC) can induce a prostate-specific immune response in androgen-modulated human prostate cancer.
OBJECTIVES: Prostate cancer recurrence, evidenced by rising prostate-specific antigen (PSA) levels after radical prostatectomy, is an increasingly prevalent clinical problem in need of new treatment options. Preclinical studies have suggested that for tumors in general, settings of minimal cancer volume may be uniquely suitable for recombinant vaccine therapy targeting tumor-associated antigens. A clinical study was undertaken to evaluate the safety and biologic effects of vaccinia-PSA (PROSTVAC) administered to subjects with postprostatectomy recurrence of prostate cancer and to assess the feasibility of interrupted androgen deprivation as a tool for modulating expression of the vaccine target antigen, as well as detecting vaccine bioactivity in vivo. METHODS: A limited Phase I clinical trial was conducted to evaluate the safety and biologic effects of vaccinia-PSA administered in 6 patients with androgen-modulated recurrence of prostate cancer after radical prostatectomy. End points included toxicity, serum PSA rise related to serum testosterone restoration, and immunologic effects measured by Western blot analysis for anti-PSA antibody induction. RESULTS: Toxicity was minimal, and dose-limiting toxicity was not observed. Noteworthy variability in time required for testosterone restoration (after interruption of androgen deprivation therapy) was observed. One subject showed continued undetectable serum PSA (less than 0.2 ng/mL) for over 8 months after testosterone restoration, an interval longer than those reported in previous androgen deprivation interruption studies. Primary anti-PSA IgG antibody activity was induced after vaccinia-PSA immunization in 1 subject, although such antibodies were detectable in several subjects at baseline. CONCLUSIONS: Interrupted androgen deprivation may be a useful tool for modulating prostate cancer bioactivity in clinical trials developing novel biologic therapies. Immune responses against PSA may be present among some patients with prostate cancer at baseline and may be induced in others through vaccinia-PSA immunization.
Androgen Antagonists↗
Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group.
To compare two popular strategies for intensifying treatment for hypertension, a double-blind, randomized, prospective, parallel-group, and partial crossover study was done. After 2 weeks of placebo run-in (baseline) and 3 weeks of 5 mg enalapril once daily, 217 patients were randomized to 6 weeks of treatment with either a low-dose combination therapy (5 mg enalapril + 5 mg felodipine ER once daily, Lexxel, Astra Merck, Inc.), or a higher dose of monotherapy (10 mg enalapril once daily, Vasotec, Merck & Co., Inc.). The group randomized to the combination had significantly greater reductions in sitting systolic/diastolic blood pressure (BP)--14.2/10.6 mm Hg compared with baseline versus 9.6/7.4 mm Hg (P < .05/.01)--as well as a greater percentage of patients having achieved either diastolic BP < 90 mm Hg or a decline of at least 10 mm Hg (responders), 59% v 41% (P < .01). When patients originally taking 10 mg enalapril were crossed over to the combination therapy for a further 6 weeks, there was a further BP reduction and increase in response rate, with loss of significant differences compared with those treated continuously with the combination for the entire 12 weeks. The greater BP-lowering efficacy of the combination was independent of age, gender, and race. There were no significant differences in tolerability between the regimens. These data support the hypothesis that in patients who do not achieve goal BP reduction with a low dose of an antihypertensive agent, a combination of two drugs with complementary mechanisms of action is more effective than increasing the dose of the first agent.
Aged↗
Idiopathic paroxysmal atrial fibrillation induced by a focal discharge mechanism in the left superior pulmonary vein: possible roles of the ligament of Marshall.
INTRODUCTION: The origin of double potentials inside the left superior pulmonary vein and their relation to the mechanisms of idiopathic paroxysmal focal atrial fibrillation (AF) are unclear. METHODS AND RESULTS: A total of 40 patients were studied. Group I included 15 patients who underwent radiofrequency catheter ablation of accessory pathway. Double potentials were found inside the left superior pulmonary vein during sinus rhythm in 10 patients and during premature atrial contractions in the remaining five patients. Group II included 25 patients with idiopathic paroxysmal AF. Double potentials were also identified in the left superior pulmonary vein. In 15 patients (Group IIA), the earliest automatic discharge during premature atrial contractions and at the onset of AF was within the left superior pulmonary vein. AF was ablated by radiofrequency energy application at the site registering double potentials. Radiofrequency ablation in the remaining 10 patients failed to terminate AF (Group IIB). The patients in Group IIA had significantly more male patients and more frequent premature atrial contractions and atrial tachycardia on 24-hour Holter recordings prior to the procedure than patients in Group IIB. CONCLUSIONS: Double potentials are present at the left superior pulmonary veins in patients with and without a history of AF. The first potential is due to the activation of atrial myocardium and the second is due to the activation of a different muscular structure. Rapid discharge of this structure triggers episodes of paroxysmal AF. Patients with focal AF originating from the left superior pulmonary vein can be identified by Holter recordings.
Action Potentials↗
Reentrant wavefronts in human ventricular tissue.
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Body Surface Potential Mapping↗