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Biomedical subjects

D Faigel

Publications and source records attributed to D Faigel.

10 recordsLinked to original sources

The accuracy of PillCam ESO capsule endoscopy versus conventional upper endoscopy for the diagnosis of esophageal varices: a prospective three-center pilot study.

BACKGROUND AND STUDY AIMS: Variceal bleeding is a major complication of cirrhosis, and is associated with a 20 % mortality at 6 weeks. Current international guidelines recommend that patients with cirrhosis are screened by conventional upper endoscopy (esophagogastroduodenoscopy, EGD) in order to detect esophageal varices. The recently developed PillCam ESO esophageal capsule endoscope has been shown to be an accurate diagnostic tool in the investigation of patients with gastroesophageal reflux and Barrett's esophagus. We compared the PillCam ESO capsule endoscope with EGD for the detection of esophagogastric varices and portal hypertensive gastropathy in patients with cirrhosis. PATIENTS AND METHODS: A pilot trial was conducted at three sites. Patients with cirrhosis who were undergoing clinically indicated EGD for screening or surveillance for esophageal varices underwent a PillCam ESO study followed by an EGD within 48 hours. Capsule videos were assessed by an investigator who was blinded to the patient's medical history and EGD findings. RESULTS: A total of 23 of the 32 enrolled patients were found to have esophageal varices at both EGD and PillCam ESO endoscopy. In one patient PillCam ESO detected small varices that were not seen at EGD. The overall concordance between PillCam ESO and EGD was 96.9 % for the diagnosis of esophageal varices and 90.6 % for the diagnosis of portal hypertensive gastropathy. There were no adverse events related to PillCam ESO endoscopy. CONCLUSIONS: In a high-prevalence population, PillCam ESO may represent an accurate noninvasive alternative to EGD for the detection of esophageal varices and portal hypertensive gastropathy. A large-scale trial is underway to validate and expand these findings.

Endoscopes, Gastrointestinal↗

Fine-needle aspiration biopsy diagnosis of gastrointestinal stromal tumors using morphology, immunocytochemistry, and mutational analysis of c-kit.

BACKGROUND: Differentiating gastrointestinal stromal tumors (GISTs) from other intramural mesenchymal tumors of the GI tract on fine-needle aspiration biopsies (FNABs) is difficult. Recent studies have shown that GISTs are immunophenotypically and genetically distinct. GISTs exhibit consistent immunohistochemical expression of CD-117 (KIT) and often express activating mutations of this protooncogene. The aim of the current study was to employ immunocytochemistry and mutational analysis of the c-kit gene to aid in the diagnosis of GISTs on FNAB. METHODS: Five endoscopic ultrasound-guided FNABs of gastrointestinal spindle cell neoplasms performed at the Veterans Affairs Medical Center (VAMC) in Portland, Oregon, from 1998-1999 were reviewed. A panel of immunocytochemical stains was performed on each cellblock including CD-117 (KIT), smooth muscle actin (SMA), desmin, S-100, and CD34. Genomic DNA (gDNA) was extracted, and amplification of exons 9, 11, 13 and 17 of c-kit was performed by polymerase chain reaction (PCR) on CD-117 (KIT) and CD34 positive cases. Direct sequencing of amplicons identified the mutations. RESULTS: Five patients were diagnosed with GISTs based on morphology and immunocytochemical positivity for CD-117 and CD34. PCR analysis of c-kit exon 11 revealed three cases with novel-sized PCR bands in addition to the expected wild-type-sized PCR product. Amplicons from these cases contained an in-frame deletion mutation. One of the two cases with wild-type-;sized exon 11 amplicons was found to be heterozygous for a point mutation producing an amino acid substitution (W557R). No mutations in exon 9, 11, 13, or 17 of c-kit were found in the remaining case. CONCLUSIONS: Ancillary techniques such as immunocytochemistry and c-kit gene mutational analysis may aid in the diagnosis of GISTs on FNABs.

Aged↗

Outcomes of Helicobacter pylori treatment in community practice and impact of therapeutic effectiveness information on physician behaviour.

BACKGROUND: The effect of knowledge of Helicobacter pylori eradication rates on physician choice of treatment regimen is unknown. As practice variation results in differences in outcome, it is important to determine whether physician behaviour can be altered by such knowledge. AIMS: (i) To determine whether dissemination of practice variation and effectiveness data regarding H. pylori changes subsequent prescribing behaviour and (ii) whether this change results in an improvement in the effectiveness of therapy. METHODS: Community gastroenterologists in the Portland metropolitan area enrolled patients being treated for H. pylori. The regimen used, diagnostic method, indication and success in eradication was measured. Patient-centred factors were also measured, including symptoms, interest in post-treatment diagnostic testing and willingness to pay. RESULTS: Significantly more physicians participating in both studies used proton pump inhibitor-triple therapy based regimens in this trial (46% vs. 85%, P=0.01), although the overall difference between the two trials was not significant (62% vs. 83%, P=0.11). There was no change in overall eradication rates by per protocol analysis between trials (84% vs. 85%, P=0.78), but a significant decrease in effectiveness by intention-to-treat analysis observed in this study (80% vs. 71%, P=0.03). Significantly more patients were treated for reasons other than peptic ulcer disease in this study (P=0.0003). CONCLUSIONS: The overall effectiveness of H. pylori therapy in practice remains good. There has been a shift in the choice of treatment regimen and indication for therapy between the time periods of the two studies. Dissemination of treatment data appears to effect prescribing behaviour, but whether it has a beneficial effect on treatment outcome remains unproven.

Anti-Bacterial Agents↗

Effective and safe endoscopic reversal of nondysplastic Barrett's esophagus with thermal electrocoagulation combined with high-dose acid inhibition: a multicenter study.

BACKGROUND: Barrett's esophagus is a metaplastic change in the esophageal lining with an increased risk for adenocarcinoma. Multiple endoscopic techniques have been applied in an effort to reverse Barrett's. This is a multicenter trial defining the efficacy and safety of multipolar electrocoagulation combined with high-dose acid inhibition. METHODS: Patients with a 2- to 6-cm segment of Barrett's esophagus without dysplasia were enrolled at 3 centers. They were treated with omeprazole 40 mg twice daily and then with up to 6 sessions with electrocoagulation aimed at eliminating all the endoscopically apparent Barrett's. Four quadrant large-capacity biopsies every 2 cm were centrally assessed for residual intestinal metaplasia. RESULTS: Fifty-eight patients reached the endpoint of failure of visual reversal of Barrett's after 6 treatment sessions or a 6-month follow-up after the last session. Eighty-five percent had visual reversal and 78% both visual and histologic reversal. Four patients had histologic evidence of residual intestinal metaplasia. Transient esophageal symptoms were common. One patient developed a stricture requiring dilation and one required overnight hospitalization for chest pain. CONCLUSIONS: The majority of patients with 2 to 6 cm of nondysplastic Barrett's esophagus can be safely reversed with this combination therapy. Long-term follow-up will be necessary to document the durability of the new squamous epithelium.

Adult↗

A randomized trial of lansoprazole, amoxycillin, and clarithromycin versus lansoprazole, bismuth, metronidazole and tetracycline in the retreatment of patients failing initial Helicobacter pylori therapy.

BACKGROUND/AIM: 10-30% of the patients treated for Helicobacter pylori fail to clear the infection after initial therapy. Little is known as to the efficacy of retreatment regimens in these patients. Proton pump inhibitor (PPI) -based triple and quadruple therapies demonstrate efficacies of 80-90% as initial therapy for H. pylori infection, but whether these regimens are as effective when used for retreatment is unknown. The efficacy of a metronidazole-containing regimen in this situation is also unknown. Our aim was to compare the efficacy of a nonmetronidazole-containing PPI-based triple versus a PPI-based quadruple therapy containing metronidazole in patients failing previous H. pylori therapy. METHODS: 48 patients were enrolled in this study at two sites after failure of previous H. pylori therapy as determined by a positive (14)C-urea breath test. Patients were stratified by prior treatment with a metronidazole-containing regimen and were then randomized to either lansoprazole (L) 30 mg twice daily, amoxycillin (A) 1,000 mg twice daily, and clarithromycin (C) 500 mg twice daily for 14 days (LAC) or L 30 mg four times daily, bismuth subsalicylate (B) 2 tablets four times daily, metronidazole (M) 250 mg four times daily and tetracycline (T) 250 mg four times daily for 14 days (LBMT). Side effects and compliance (pill count) were assessed at the completion of therapy. A repeat (14)C-urea breath test was performed 4 or more weeks after completion of therapy, and cure was defined as a negative test result. RESULTS: 48 patients (16 males and 32 females) were enrolled in this study. 20 patients received LAC (18 prior M), and 28 received LBMT (23 prior M). Per protocol and intention-to-treat efficacies were 82% (95% CI 64-100%) and 75% (95% CI 56-94%) for LAC and 80% (96% CI 64-96%) and 71% (95% CI 54-88%) for LBMT (p = 0.85 per protocol and p = 0.78 intention to treat between LAC and LBMT), respectively. The compliance (> or =80% of pills taken) was found to be 89% in both treatment groups. Side effects were noted in 84% for LAC and in 82% for LBMT, but were mild and did not cause discontinuation of therapy. CONCLUSIONS: PPI-based triple and quadruple therapy with both LAC and LBMT are effective in retreating patients failing initial metronidazole-based H. pylori therapies. LAC was not statistically superior to LBMT as a 'retreatment' regimen in this clinical situation, but the small sample size and wide confidence limits do not preclude the possibility of a smaller but significant difference in efficacy between the regimens. To determine whether LAC or LBMT is as effective for retreating patients failing non-metronidazole-containing regimens requires further study.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Fingerstick Helicobacter pylori antibody test: better than laboratory serological testing?

OBJECTIVE: Antibody testing is the recommended method to screen for Helicobacter pylori (H. pylori) infection. Whole-blood fingerstick antibody tests are simple, in-office tests providing rapid results, but the accuracy of first-generation tests was lower than other diagnostic tests. We assessed a new whole-blood antibody test, using endoscopic biopsy tests as a "gold standard," and compared it with a laboratory quantitative serological test. METHODS: Two hundred-one patients not previously treated for H. pylori who were undergoing endoscopy had gastric biopsies for rapid urease test and histological examination; whole-blood antibody tests and quantitative serological tests were also performed. Two separate gold standards for H. pylori infection were employed: either rapid urease test or histological exam positive; and both rapid urease test and histological exam positive. RESULTS: Sensitivities for whole-blood test versus quantitative serology with gold standard 1 (either biopsy test positive) were 86% versus 92% (95% confidence interval [CI] of difference, -2-14%; p = 0.19) and specificities were 88% versus 77% (95% CI of difference, 0.4-22%; p = 0.052). Sensitivities with gold standard 2 (both biopsy tests positive) were 90% versus 94% (95% CI of difference, -4-12%; p = 0.41) and specificities were 79% versus 67% (95% CI of difference, 1-24%; p = 0.048). CONCLUSIONS: New generation in-office, whole-blood antibody tests that can achieve a sensitivity and specificity similar to or better than those of widely used quantitative laboratory serological tests may be used as the initial screening tests of choice for H. pylori.

Adult↗

Vitamin E supplementation effect on human platelet function, arachidonic acid metabolism, and plasma prostacyclin levels.

A randomized, placebo-controlled double-blind trial was conducted on 20 adults to assess the effect of vitamin E (800 IU/d 727 mg/d for 5 wk) on platelet function, arachidonic acid metabolism, and prostacyclin generation. Platelet aggregation was measured in response to collagen, arachidonic acid, and adenosine diphosphate. Thromboxane B2 was assayed in serum and in the supernatant plasma after platelet aggregation. Platelets were labeled with [3H]arachidonic acid to assess production and release of cyclooxygenase products (MDA, TXB2, and HHT), a lipoxygenase product (12-HETE), and arachidonic acid in response to stimulation by thrombin or collagen. Prostacyclin was measured in plasma and in blood collected from bleeding-time incisions by a sensitive HPLC-RIA procedure. Despite marked increases in plasma and erythrocyte vitamin E levels in the vitamin E group, there were no significant differences between the vitamin E and placebo groups in any of the variables measured.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Low-dose enteric-coated aspirin: a practical approach to continuous-release low-dose aspirin and presystemic acetylation of human platelet cyclooxygenase.

Using a granular enteric-coated aspirin (ECA) preparation, we achieved continuous release of low-dose aspirin and associated inhibition of platelet reactivity. The lowest once-daily dose that produced greater than 90% inhibition of serum thromboxane (TX) A2 after 7 days was 80 mg. The time course of inhibition after the first dose indicated a gradual release of aspirin over a period of 8 hours. We subsequently fractionated this 80 mg dose into three times daily doses of 27 mg that were administered to nine healthy men for 7 days. This regimen resulted in 96% inhibition of serum TXA2 generation (P less than 0.001), inhibition of in vitro platelet aggregation (P less than 0.05), prolongation of the bleeding time by 75% (P less than 0.01), and a threefold increase in inhibition of platelet aggregation by prostacyclin (P less than 0.01) compared with pre-ECA values. In contrast to our previous study using daily 80 mg doses of ECA, after the 27 mg three times daily regimen we found a significant increase in circulating platelet cyclooxygenase activity 24 hours after the final dose (P less than 0.05). This immediate recovery indicates active megakaryocyte cyclooxygenase and suggests that acetylation of platelet cyclooxygenase was restricted to the presystemic circulation. We conclude that long-term dosing with 27 mg ECA three times daily results in profound inhibition of platelet TXA2 production, and diminished in vitro and in vivo platelet reactivity. This regimen provides a practical approach to achieving continuous release of low-dose aspirin and possible presystemic acetylation of platelet cyclooxygenase.

Acetylation↗