The Effect of Nb, Ta, and Ti on the Oxidation of a New Polycrystalline Ni-Based Superalloy.

The effect of variations in Nb, Ta, and Ti concentrations in exchange for Al on the oxidation resistance of a new polycrystalline Ni-based superalloy (C19) was studied in air at 800 °C for up to 1000 h. An external scale of Ti-doped Cr2O3 and a sub-scale of discontinuous Al2O3 intrusions formed on the surface of all the studied alloys. Contrary to other reports, increasing the Nb concentration improved the oxidation performance and may have promoted the formation of a CrTaO4 layer, thereby reducing oxygen ingress. The addition of Ta also significantly improved oxidation resistance and reduced the depth of the Al2O3 intrusions. Increasing the Ti concentration did not significantly affect the oxidation performance, potentially due to the relatively low Ti concentrations investigated. Several of the studied alloys with modified Ta and Ti concentrations showed regions of continuous Al2O3 scale formation, suggesting that the compositions are in a transition regime between Cr2O3-forming and Al2O3-forming behaviour. The findings suggested that part of the Ti content in C19 could potentially be replaced with Nb, Ta and/or other elements to further enhance oxidation resistance and other desirable properties. Overall, the insights gained could serve as a guide to optimise the composition of C19 and similar alloys for enhanced oxidation resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10218-7.

Evaluating Wagner Oxidation Criteria for Protective Al2O3 Scale Formation in Ni-Based Superalloys.

An assessment is made of the Wagner transition criteria for predicting the formation of a continuous Al2O3 scale in Ni-based superalloys. Predictions are compared with data from an experimental Ni-based superalloy as well as commercial superalloys for which published data are available. The methodology was generally successful in predicting the transition temperature of the commercial superalloys but underpredicted the transition temperature of the experimental superalloy by approximately 50-100 °C. The difference in the transition temperature of the experimental superalloy to form a continuous Al2O3 scale is primarily attributed to a complex oxide subscale that increased the internal volume fraction of oxide and led to reduced oxygen ingress. The sensitivity and limitations of the methodology are discussed, and recommendations are made to refine the methodology to facilitate the interpretation of oxidation behaviour in polycrystalline Ni-based superalloys. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10163-5.

Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa.

BACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα+ cells without a significant change in ICCs.

Study on the effect of different doses of rosuvastatin on ventricular remodeling in patients with acute coronary syndrome after emergency percutaneous coronary intervention.

OBJECTIVE: The objective of the present study was to observe the effects of different doses of rosuvastatin on cardiac protection in patients with acute coronary syndrome (ACS) after stent implantation. PATIENTS AND METHODS: A total of 137 patients with ACS were selected from March 2014 to January 2015 and randomly divided into: 1. The conventional treatment group: 45 patients were treated with conventional drugs such as aspirin, clopidogrel, nitrates, and a ß-blocker; 2. The conventional rosuvastatin dose group: 45 patients received 10 mg/d rosuvastatin before sleep in addition to routine therapy; 3. The large rosuvastatin dose group: 47 patients received 20 mg/d rosuvastatin before sleep in addition to routine therapy. The course of treatment was 12 weeks. At 1, 6, and 12 week, ultrasound echocardiography, electrocardiogram (ECG), high-sensitivity C-reactive protein (hs-CRP), and pro-brain natriuretic peptide (pro-BNP) levels were tested to evaluate the therapeutic effects. The ultrasonic imaging criteria included left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), and left ventricular ejection fraction (LVEF). RESULTS: After 1 week, hs-CRP, pro-BNP, and echocardiography of the patients in the three groups showed no significant differences (p>0.05); after 6 and 12 weeks, the levels of hs-CRP, MMP-9, and pro-BNP in the large rosuvastatin dose group were significantly lower than in the conventional rosuvastatin dose group and conventional treatment group (p<0.05), and ultrasonic indexes changed significantly after 12 weeks (p<0.05). There were no significant differences in ultrasonic indexes after 6 weeks (p>0.05). No thrombosis or restenosis occurred during the follow-up period in each group. CONCLUSIONS: Three months after emergency percutaneous coronary intervention, a high-dose of rosuvastatin can delay ventricular remodeling, effectively inhibit malignant remodeling of the heart, improve left ventricular systolic function, reduce the prevalence of adverse events, and significantly improve the long-term prognosis.

A retrospective comparison of neoadjuvant chemoradiotherapy regimens for locally advanced esophageal cancer.

Preoperative chemoradiotherapy (CRT) with carboplatin/paclitaxel has been shown to increase survival in patients with esophageal cancer, including gastroesophageal junction (GE) junction cancer, over surgery alone; however, there have been no studies comparing the different neoadjuvant CRT regimens. We retrospectively evaluated the long-term results of trimodality therapy for patients with locally advanced esophageal cancer treated on several chemotherapy regimens. Between 1999 and 2014, 215 patients with locally advanced esophageal cancer underwent neoadjuvant CRT followed by surgical resection. The median age was 62 years (range 21-84), 80.5% were men and 86% had adenocarcinoma. The following chemotherapy regimens were administered: cisplatin/5FU (14.9%), cisplatin/irinotecan (35.8%), carboplatin/paclitaxel (35.8%), and other (9.7%). The majority of patients (92.1%) received a radiation dose of 50.4 Gy. Predictors of toxicities and surgical complications were assessed using logistic regression. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier method and proportional hazards regression was used to model time-to-event outcomes. The median follow-up among surviving patients was 4.1 years (range 0.4,13). The median OS was 3.0 years from time of diagnosis and OS was 36.8% at 5 years. RFS was 34.9% at 5 years. After neoadjuvant CRT, 34.7% of patients achieved a pathologic complete response including 60.7% of squamous cell carcinoma patients and 18.4% of adenocarcinoma patients (P < 0.001) and 66% were downstaged. Of the variables examined, pathologic stage, preoperative baseline cardiac comorbidity, postoperative cardiac or pulmonary complications, and chemotherapy regimen were associated with OS. Using cisplatin and 5FU as the reference regimen, patients treated with carboplatin/paclitaxel had significantly improved OS (HR = 0.47, P = 0.017 after adjusting for surgery type, radiation modality, baseline cardiac comorbidity, and preoperative stage) with 5-year OS rate of 66%. The most common surgical complications were cardiac in 61 patients (28.5%) and pulmonary in 52 patients (24.3%). Cardiac complications were associated with age (OR 1.05, P = 0.007) and cardiac comorbidity (OR 2.6, P = 0.02) and pulmonary complications with female gender (OR 3.98, P < 0.001). Forty-four patients (20.5%) required readmission within 30 days of discharge, and readmission was associated with cardiac comorbidity (OR 2.7, P = 0.017). Three patients died within 30 days of surgery. We observed an association between neoadjuvant carboplatin/paclitaxel and improved overall survival that requires confirmation in a prospective randomized trial.

The Impact of Pathologic Complete Response in Patients with Neoadjuvantly Treated Locally Advanced Rectal Cancer-a Large Single-Center Experience.

Small cohort studies demonstrated better oncologic outcomes for patients with pathologic complete response (PathCR) after neoadjuvant treatment for locally advanced rectal cancer. This study reviews long-term outcomes of a large cohort of clinically stage II/III rectal cancer patients who received neoadjuvant chemoradiation and surgery. This is a retrospective analysis of a single-center cohort, including all clinical stage II/III rectal cancer patients who received neoadjuvant chemoradiation and surgery between 2004 and 2014 (n = 271). Cox regressions were done to assess the influence of PathCR on recurrence-free survival (RFS) and overall survival (OS), adjusting for postoperative chemotherapy, clinical AJCC staging, comorbidity, and age where appropriate. PathCR patients had significantly lower distant recurrence rates (4 vs. 15.8%; P = 0.028) and lower disease-specific mortality rates (0 vs. 8.1%; P = 0.052), compared to patients with residual disease. PathCR was associated with longer RFS (HR, 5.6 [95% CI 1.3-23.1] P = 0.018) and longer OS (HR, 3.4 [1.31-10.0] P = 0.014) compared to having pathological residual disease. This large single-center study shows that patients with PathCR have significant longer RFS and OS than patients with residual disease on pathology after neoadjuvant chemoradiation.

Most children with eosinophilic esophagitis have a favorable outcome as young adults.

The disease progression of eosinophilic esophagitis (EoE) from childhood into adulthood is unclear. To determine the clinical outcome of patients who were diagnosed with EoE as children, and who now are young adults. Children (<18 years old) diagnosed with EoE were enrolled in a prospective registry on demographics, presenting symptoms, and endoscopic/histologic findings. Subjects who now are adults (≥18 years old) were identified, and a structured telephone interview was conducted to obtain follow-up data on symptom prevalence (dysphagia to solids and liquids, nausea/vomiting, abdominal pain, and heartburn/regurgitation), food impaction, medication usage, health-care utilization, and resolution of atopy/food allergies. A favorable outcome was defined if EoE symptoms were resolved or improved by subjects' assessment. Unfavorable outcomes was defined as symptoms same or worse. Clinical variables that predicted a favorable outcome as an adult were examined. Mayo Dysphagia Scale (MDQ-30: scored 0-100) was administered to validate the outcome assessment. Mantel-Haenszel odds ratio and unpaired t-test were used. Fifty-eight subjects (64% male) who met study criteria were enrolled. Mean age at diagnosis was 12 years (range 4-17) and mean duration of follow-up was 8.3 years (2-16). As children, the most common presenting symptoms were abdominal pain (54%), dysphagia (33%), and vomiting (24%). As young adults, 47 subjects (81%) had a favorable outcome. Total MDQ-30 scores were 4.6 (0-30) and 14.1 (0-50) in subjects with favorable outcome and unfavorable outcome, respectively (P = 0.015). Two-thirds of subjects did not use steroids or proton pump inhibitors in the preceeding 12 months. Male children with EoE were four times more likely to have a favorable outcome as young adults compared with female children. Females were more likely to report nausea/vomiting as young adults (odds ratio 3.23, CI 0.97-10.60). Of all presenting symptoms in EoE children, dysphagia was the most likely to persist into adulthood (odds ratio 6.29, CI 1.85-21.38). Eighty one percent of EoE children had a favorable outcome as young adults. Most patients with symptom resolution did not require any form of steroid therapy or seek healthcare.

Association between Serum Total Osteocalcin Level and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Studies on the association between serum total osteocalcin level and type 2 diabetes mellitus (T2DM) had reported controversial results. The aim of this study was to comprehensively assess this association through a meta-analysis. Eligible articles were identified in electronic databases from their inception through May 1, 2015. To assess the relationship between serum total osteocalcin and T2DM, a meta-analysis was performed to determine whether total osteocalcin differed obviously between individuals with and without T2DM, and whether serum total osteocalcin level was associated with the risk of T2DM. The standardized mean difference (SMD) and their 95% confidence intervals (95% CIs) for total osteocalcin between individuals with and without T2DM, and pooled odds ratios (ORs) and their 95% CI for the T2DM risk were calculated by meta-analysis. Twenty-four papers fulfilled the inclusion criteria. From the pooled data, the total osteocalcin level was significantly lower among T2DM patients than controls (SMD: - 2.87; 95% CI-3.76 to - 1.98; p<0.00001), and high total osteocalcin level was significantly and independently associated with decreased risk of T2DM (OR=0.70, 95% CI 0.56-0.88; p=0.002). There was no evidence for publication bias. Serum total osteocalcin level is significantly lower in T2DM patients than controls, and total osteocalcin is inversely associated with the development of T2DM.

Gastric electrical stimulation with Enterra therapy improves symptoms of idiopathic gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) is a therapeutic option for intractable symptoms of gastroparesis (GP). Idiopathic GP (ID-GP) represents a subset of GP. AIMS: A prospective, multicenter, double-blinded, randomized, crossover study to evaluate the safety and efficacy of Enterra GES in the treatment of chronic vomiting in ID-GP. METHODS: Thirty-two ID-GP subjects (mean age 39; 81% F, mean 7.7 years of GP) were implanted with GES. The stimulator was turned ON for 1½ months followed by double-blind randomization to consecutive 3-month crossover periods with the device either ON or OFF. ON stimulation was followed in unblinded fashion for another 4.5 months. Twenty-five subjects completed the crossover phase and 21 finished 1 year of follow-up. KEY RESULTS: During the unblinded ON period, there was a reduction in weekly vomiting frequency (WVF) from baseline (61.2%, P < 0.001). There was a non-significant reduction in WVF between ON vs OFF periods (the primary outcome) with median reduction of 17% (P > 0.10). Seventy-five percent of patients preferred the ON vs OFF period (P = 0.021). At 1 year, WVF remained decreased (median reduction = 87%, P < 0.001), accompanied by improvements in GP symptoms, gastric emptying and days of hospitalization (P < 0.05). CONCLUSIONS & INFERENCES: (i) In this prospective study of Enterra GES for ID-GP, there was a reduction in vomiting during the initial ON period; (ii) The double-blind 3-month periods showed a non-significant reduction in vomiting in the ON vs OFF period, the primary outcome variable; (iii) At 12 months with ON stimulation, there was a sustained decrease in vomiting and days of hospitalizations.

A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis.

BACKGROUND: Gastroparesis causes significant morbidity and treatment options are limited. TZP-102 a novel, macrocyclic, selective, oral ghrelin receptor agonist, was evaluated in a randomized, double-blind, placebo-controlled trial in patients with diabetic gastroparesis. METHODS: A total of 92 outpatients were randomized to once-daily administrations of 10-mg (n = 22), 20-mg (n = 21), 40-mg (n = 23) TZP-102 or placebo (n = 26). The primary endpoint was the change from baseline in gastric half-emptying time (T(½)) utilizing (13)C-breath test methodology and secondary endpoints included symptom improvement using patient-reported gastroparesis symptom scores (PAGI-SYM questionnaire) and patient and physician overall treatment evaluations (OTE). KEY RESULTS: Gastric T½ changes were not statistically significant between TZP-102 and placebo after 28 days of treatment at any dose. Clinical improvements (-1.0 to -1.4 point mean decrease in symptom severity) occurred in the Gastroparesis Cardinal Symptom Index (GCSI) component of the PAGI-SYM, which was significant vs placebo for all TZP-102 doses combined. Improvements became evident after 1 week of treatment. Significantly, more patients given TZP-102 (any dose) had a 50% reduction in baseline GCSI score (28.8%vs 7.7% placebo). Safety profiles were similar across groups. All TZP-102 doses were well-tolerated with no adverse cardiac, weight, or glucose control outcomes. CONCLUSIONS & INFERENCES: TZP-102 for 28 days, at doses of 10-40 mg once daily, was well-tolerated and resulted in a reduction in symptoms of gastroparesis. The lack of correlation between symptom improvement and gastric emptying change is consistent with previous studies in diabetic gastroparesis, and emphasizes the value of patient-defined outcomes in determining therapeutic benefit.

Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data.

BACKGROUND: Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and malnutrition due to inadequate caloric and fluid intake. TZP-101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis. AIM: To assess effects of TZP-101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of ≥3.5 (range: 0-5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale. METHODS: Patients were hospitalised and received four single daily 30-min infusions of one of six TZP-101 doses (range 20-600 µg/kg) or placebo. Efficacy was assessed by symptom improvement. RESULTS: At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45±0.44. Statistically significant improvements over placebo occurred in the 80 µg/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of -3.82±0.76, P=0.011) and the GCSI Total score (-3.14±0.78, P=0.016) and were maintained at the 30-day follow-up assessment (-2.02±1.63, P=0.073 and -1.99±1.33, P=0.032 respectively). The proportion of days with vomiting was reduced significantly (P=0.05) in the 80 µg/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days). CONCLUSIONS: TZP-101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP-101, supporting further investigation of TZP-101 in the management of severe gastroparesis.

Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study.

BACKGROUND: Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. METHODS: Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 µg kg(-1) TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. KEY RESULTS: The 80 µg kg(-1) dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 µg kg(-1) dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 µg kg(-1) TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 µg kg(-1) group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated. CONCLUSIONS & INFERENCES: TZP-101 appears to be safe, well-tolerated, and effective at acutely addressing several gastroparesis symptoms.

Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule.

BACKGROUND: The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. METHODS: Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI = Ln (Ct *sum amplitudes +1)) were analyzed for 60 min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. KEY RESULTS: Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P < 0.05). Median values of the motility parameters in gastric window were Ct = 72, MI = 11.83 for healthy and Ct = 47, MI = 11.12 for gastroparetics. In the small bowel, median values were Ct = 144.5, MI = 12.78 for healthy and Ct = 93, MI = 12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. CONCLUSIONS & INFERENCES: The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.

Pharmacokinetic profile of immediate-release omeprazole in patients with gastro-oesophageal reflux associated with gastroparesis.

BACKGROUND: Immediate-release omeprazole has a more rapid absorption compared with delayed-release omeprazole in asymptomatic volunteers. However, effects of delayed gastric emptying on omeprazole absorption remain unknown. AIM: To compare pharmacokinetics between immediate and delayed-release omeprazole in patients with GERD associated with gastroparesis. METHODS: Open-label, randomized, cross-over study was performed. Antireflux and prokinetic medications were discontinued. Subjects were randomized into: (i) Immediate-release omeprazole 40 mg suspension o.m. for 7 days, wash-out for 10-14 days, followed by delayed-release omeprazole 40 mg capsule o.m. for 7 days, or (ii) the same schedule in reverse order. On day 7, omeprazole concentrations were obtained before and up to 5 h after taking the study drug. Patient Assessment of GI Disorders-Symptom Severity Index was obtained. RESULTS: A total of 12 women (mean age 51 years) completed the protocol. Time to maximal omeprazole concentration was significantly shorter for omeprazole. Maximal concentration was significantly greater for omeprazole, but total area under concentration-time curves was similar. Pharmacokinetic profile was less variable for immediate compared with delayed-release omeprazole. CONCLUSIONS: Immediate-release omeprazole was associated with a more rapid absorption and less variable pharmacokinetic profile compared with delayed-release omeprazole in reflux patients associated with gastroparesis.

Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects.

BACKGROUND: Gastric emptying scintigraphy (GES) using a radio-labelled meal is used to measure gastric emptying. A nondigestible capsule, SmartPill, records luminal pH, temperature, and pressure during gastrointestinal transit providing a measure of gastric emptying time (GET). AIMS: To compare gastric emptying time and GES by assessing their correlation, and to compare GET and GES for discriminating healthy subjects from gastroparetics. METHODS: Eighty-seven healthy subjects and 61 gastroparetics enrolled with simultaneous SmartPill and GES. Fasted subjects were ingested capsule and [(99m)Tc]-SC radio-labelled meal. Images were obtained every 30 min for 6 h. Gastric emptying time and percentage of meal remaining at 2/4 h were determined for each subject. The sensitivity/specificity and receiver operating characteristic analysis of each measure were determined for each subject. RESULTS: Correlation between GET and GES-4 h was 0.73 and GES-2 h was 0.63. The diagnostic accuracy from the receiver operating characteristic curve between gastroparetics and healthy subjects was GET = 0.83, GES-4 h = 0.82 and GES-2 h = 0.79. The 300-min cut-off time for GET gives sensitivity of 0.65 and specificity of 0.87 for diagnosis of gastroparesis. The corresponding sensitivity/specificity for 2 and 4 h standard GES measures were 0.34/0.93 and 0.44/0.93, respectively. CONCLUSION: SmartPill GET correlates with GES and discriminates between healthy and gastroparetic subjects offering a nonradioactive, standardized, ambulatory alternative to scintigraphy.

Totally laparoscopic feeding jejunostomy.

BACKGROUND: A feeding jejunostomy should be used for nutritional support in a small subset of patients. Minimal-access approaches for the placement of jejunal tubes have been described, but they often require special equipment not common to all operating theaters. We describe a technique of totally laparoscopic jejunostomy tube (LJT) placement using equipment found in most operating theaters. METHODS: Thirty-five patients underwent LJT over a 12-month period. Indications included gastroparesis, anorexia nervosa, oral cancer, cerebral palsy, and Huntington's chorea. The technique involved three incisions for trocars (one for a 10-mm camera and two for 5-mm working ports) and one small incision for the tube. A 16-Fr T-tube was passed transabdominally under direct vision, and a jejunotomy was made approximately 20 cm distal to the ligament of Trietz. Each limb of the T-tube was passed into the lumen of the bowel, and a purse-string suture was placed around the enterotomy and tied intracorporeally. After insertion, the serosa surrounding the insertion site is tacked to the anterior abdominal wall in four places with a reusable stainless steel suture passer. To test whether the tube was watertight, we injected methylene blue solution into the tube. RESULTS: All of the patients tolerated the procedure well. There were no operative deaths. Five LJTs were electively removed in the office. One patient was reoperated on 10 days postoperatively because of intractable pain, but the source of pain was not found and the LJT was intact. CONCLUSIONS: LJT may be placed safely using the described technique. No significant morbidity or mortality occurred in our series. The results of this study have prompted us to consider LJT for any patient requiring access to the jejunum for feeding.

Comparison of methylene blue-directed biopsies and conventional biopsies in the detection of intestinal metaplasia and dysplasia in Barrett's esophagus: a preliminary study.

BACKGROUND: The diagnostic advantage of methylene blue (MB) chromoendoscopy in Barrett's esophagus is unclear. METHODS: Patients with columnar-lined esophagus (CLE) were enrolled into a prospective, randomized crossover trial of MB-directed biopsy versus conventional biopsy. RESULTS: Forty-seven patients (19 long-segment CLE; 28 short-segment CLE) were enrolled and underwent MB-directed biopsy. Sensitivity and specificity of MB for specialized intestinal metaplasia were 53% and 51%, respectively. Sensitivity and specificity of MB for dysplasia were 51% and 48%, respectively. Thirty-five patients (15 long-segment CLE; 20 short-segment CLE) completed the crossover trial. Relative frequencies for specialized intestinal metaplasia were 73% and 71% from MB-directed and conventional biopsy specimens, respectively (p = 0.73). Relative frequencies for dysplasia were 20% and 18% from MB-directed and conventional biopsy specimens, respectively (p = 0.65). In patients with long-segment CLE, dysplasia was diagnosed in 10 patients with MB and 7 patients with conventional biopsy methods (p = 0.25). The number of biopsy specimens per EGD was greater with MB, which may have influenced the diagnosis. Histologically, the grade of dysplasia was indefinite/low in nearly all of the dysplastic specimens. CONCLUSIONS: Results of MB-directed biopsy were similar to conventional biopsy in detecting specialized intestinal metaplasia and indefinite/low-grade dysplasia. MB was not useful in short-segment Barrett's esophagus.

Current medical and surgical treatment options for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common disorders in medicine. The options of medical versus surgical therapies have been highlighted by more potent acid suppression medications and by the introduction of minimally invasive surgery for GERD. Many factors will impact on the treatment selection for each individual patient: the underlying pathophysiology, typical vs atypical symptoms, presence of reflux complications, and success and limitations of medical and surgical treatments. Medical antireflux therapy is very effective and safe, but long-term maintenance therapy is required for most patients. Minimally invasive antireflux surgery has provided excellent results, but outcome is dependent on patient selection and surgical expertise. Careful pre-operative evaluation is essential to determine the optimal treatment and surgical approach.

Recipient FK506 pretreatment regimens in rat small bowel transplantation: allograft survival, function, and systemic infection.

PURPOSE: Successful small bowel transplantation requires effective immunosuppression that preserves intestinal function but avoids opportunistic infection. This study aims to evaluate FK506 as a single immunosuppressant in different pretreatment regimens in a rat high responder strain combination. METHODS: Lewis --> DA rat heterotopic small bowel transplantation was performed. Studied groups were (1) untreated control, n = 12; (2) FK-1, n = 8; (3) FK-3, n = 8. FK506 (2 mg/kg/d, intramuscularly) was given to the recipients for 1 day (FK-1) and 3 days (FK-3) before small bowel transplantation, followed by 2 weeks of subtherapeutic treatment (0.3 mg/kg/d, intramuscularly) after small bowel transplantation. Syngeneic small bowel transplantation also was performed (n = 8). FK blood levels, maltose absorption test, histology, and bacteriology were performed at different postoperative days. RESULTS: Allograft survival was prolonged significantly with FK pretreatment, being more so in FK-3 group (FK-1, 22.2 +/- 1.5 d; FK-3, 40.7 +/- 14.1 d; control, 6.6 +/- 0.8 d; P< .01). In the first postoperative week, FK blood level was significantly higher in FK-3 group (19.8 +/- 1.5 ng/mL) than in FK-1 group (5.0 +/- 0.4 ng/mL; P < .05). There was no evidence of systemic infection in either FK-treated group. For maltose absorption, control allograft was abnormal on day 7 correlating to severely damaged intestinal architecture. In contrast, FK-treated allografts showed well-protected intestinal structure and normal absorption on days 7 and 21. CONCLUSION: High FK506 blood levels in the first postoperative week, achieved with FK pretreatment, prolonged intestinal allograft survival and preserved intestinal structure and function without allowing systemic infection.