Preparation and Characterization of pH-Sensitive Anionic Hydrogel Microparticles for Oral Protein-Delivery Applications

pH-sensitive P(MAA-g-EG) anionic hydrogel microparticles having an average diameter of approx. 4 μm were prepared by suspension photopolymerization. The pH-sensitive swelling and release behaviors of the P(MAA-g-EG) hydrogel microparticles were investigated as a biological on–off switch for the design of an oral protein delivery system triggered by external pH changes in the human GI tract. There was a drastic change of the equilibrium weight swelling ratio of P(MAA-g-EG) particles at a pH of around 5, which is the pK _a of PMAA. At pH < 5, the particles were in a relatively collapsed state, while at a pH > 5 the particles swelled to a high degree. When the concentration of the cross-linker of the hydrogel increased, the swelling ratio of the P(MAA-g-EG) hydrogel microparticles decreased at a pH higher than 5 and the pK _a of all the microparticles was in the pH range 4.0–6.0. In release experiments using Rhodamine B (Rh-B) as a model solute, the P(MAA-g-EG) hydrogel microparticles showed a pH-responsive release behavior. At low pH (pH 4.0) only a small amount of Rh-B was released while at high pH (pH 6.0) a relatively large amount of Rh-B was released from the hydrogel particles.     

Role of Active Oxygen Species and Lipid Peroxidation in Mepirizole-Induced Duodenal Ulcers in Rats

The role of active oxygen species and lipidperoxidation in the pathogenesis of duodenal ulcersinduced by mepirizole was investigated in rats. Oraladministration of mepirizole (200 mg/kg) resulted in ulcer lesions in the proximal duodenum.Thiobarbituric acid-reactive substances (TBA-reactivesubstances), an indicator of lipid peroxidation, alsosignificantly increased in the duodenal mucosa.Myeloperoxidase (MPO) activity in the duodenal mucosa, a signof polymorphonuclear leukocyte (PMN) accumulation,significantly increased. Combination treatment withpolyethylene glycol-modified Serratia Mn-SOD andcatalase significantly decreased the size of the ulcersand TBA-reactive substances in the duodenal mucosa.Allopurinol, a xanthine oxidase inhibitor, also reducedthe size of duodenal ulcers. Both the size of the ulcers and the increase in TBA-reactivesubstances in the duodenal mucosa were significantlylower in PMN-depleted rats. Mepirizole increased thesurface expression of adhesion molecule CD18 on PMNs in vitro. These results suggest that lipidperoxidation, mediated by active oxygen speciesgenerated from xanthine oxidase and PMNs, plays animportant role in the pathogenesis of duodenal ulcersinduced by mepirizole.     

Intraductal Secretin Test Is as Useful as Duodenal Secretin Test in Assessing Exocrine Pancreatic Function

We assessed the clinical usefulness of theintraductal secretin test in order to ascertain whetherit can substitute for the conventional duodenal secretintest. Duodenal juice was obtained with a triple-lumen tube and pure pancreatic juice was obtained byretrograde cannulation of the main pancreatic duct usinga duodenofiberscope. Pancreatic secretion was stimulatedby a bolus intravenous injection of secretin (100 units). The two tests showed comparableinterindividual coefficients of variation, significantlygood correlations, and comparable diagnosticefficiencies. The intraductal secretin test showed noless reproducibility than that of the duodenalsecretin test as reported in the literature. In theintraductal secretin test, secretory volume, peak flowrate, bicarbonate output, and lipase output yielded the best diagnostic efficiency, followed by amylaseoutput and maximal bicarbonate concentration. In theintraductal secretin test, a 10-min collection providedas much information as a 20-min collection. We conclude, therefore, that the 10-minintraductal secretin test is as useful as theconventional duodenal secretin test in assessingexocrine pancreatic function and that the mostdiscriminatory parameters are secretory volume, bicarbonate output, andamylase (or lipase) output.     

胆囊十二指肠瘘的诊断与治疗

目的 探讨胆囊十二指肠瘘的发生机制、病理改变、诊断方法及治疗过程中的注意事项。方法 回顾性分析17年间收治的11例胆囊十二指肠瘘患者的临床资料。结果 全部经手术证实和治疗。10例继发于胆囊炎、胆囊结石；1例为溃疡病所致，仅1例于术前确诊。9例痊愈，2例死亡，均死于术后腹腔严重感染。结论 胆囊十二指肠瘘大多继发于胆囊炎和胆囊结石，多伴有胆囊萎缩、周围粘连明显等病理情况。X线检查、钡餐、ERCP等对诊断较有价值。治疗原则是切除胆囊、清除结石、切断瘘管、修补十二指肠瘘口，并根据情况探查胆总管或行胆肠内引流。     

溃疡宁治疗十二指肠球部溃疡活动期疗效观察

本文报告口服纯中药制剂溃疡宁片6周,治疗十二指肠球部溃疡活动期的近期治愈率为61.1%,总有效率为100%,消除各种症状的效果较好,与雷尼替丁对照组的疗效基本相同(P>0.05),而且未发现明显的毒副作用。同时,溃疡宁片对十二指肠球部溃疡活动期的各个中医证型的临床治愈率也基本相同(P>0.05)。提示溃疡宁片适应于十二指肠球部溃疡活动期中医各证型患者,是治疗十二指肠球部溃疡活动期有较好效果的固定方剂。     

Early Results of Laparoscopic Biliopancreatic Diversion with Duodenal Switch: A Case Series of 40 Consecutive Patients

Background: Biliopancreatic diversion with duodenal switch (BPD-DS) is an operation which provides one of the greatest maintained weight losses of any bariatric procedure.We looked at the safety and efficacy of laparoscopic BPD-DS for morbid obesity. Methods: A 150-200 ml sleeve gastrectomy was created and anastomosed to the distal 250 cm of divided ileum. The median length of the common channel was 100 cm. All patients were prospectively followed up to 12 months. Results: 40 consecutive patients underwent laparoscopic BPD-DS as a primary procedure for morbid obesity. Median patient body mass index (BMI) was 60 kg/m2 (range 42-85 kg/m2). Mean age was 43 ± 1 years (± SEM), with 12 males and 28 females. One patient was converted to open laparotomy (2.5%). Median operative time was 210 ± 9 minutes (range 110-360 minutes) with a significant correlation between BMI and operative time (p = 0.04). Median length of stay was 4 days (range 3- 210 days). There was one 30-day mortality (2.5%). Major morbidities occurred in 6 patients (15%), including 1 anastomotic leak (2.5%), 1 venous thrombosis (2.5%), 4 staple-line hemorrhages (10%) and 1 subphrenic abscess (2.5%). Median follow-up at 6 months (range 1-12 months) resulted in 46% ± 2% excess weight loss (EWL) and at 9 months 58% ± 3% EWL. Conclusion: Laparoscopic BPD-DS is a complex, yet feasible, procedure resulting in effective weight loss with an acceptable morbidity. A BMI >65 was associated with increased morbidity and mortality. A long-term study is needed to confirm efficacy and proper patient selection.     

The Biliopancreatic Diversion with the Duodenal Switch: Results Beyond 10 Years

The BPD/DS, if properly performed, has the best long-term weight loss of any bariatric operation. It is easy to reverse or revise, has the least marginal ulcers, cures the highest percentage of co-morbidities, has the least failures, and permits normal although smaller meals. It is our opinion that the BPD/DS should be considered as the gold standard bariatric operation.     

"Right-Angled" Stapled Latero-lateral Duodenojejunal Anastomosis in the Duodenal Switch

A simplified technique to perform the duodeno-enteral anastomosis in the duodenal switch is presented. A linear stapled duodeno-jejunal side-to-side anastomosis is performed. The technique is easy and rapid to perform, avoids passing an anvil through the mouth of the patient and is safe for the patient, with satisfactory short-term results.     

Longitudinal Gastrectomy as a Treatment for the High-Risk Super-Obese Patient

Background: Bariatric surgery in patients with significant co-morbid conditions is associated with increased perioperative risk. Methods: From 1995-2001, 795 patients were operated upon at our institution for the diagnosis of morbid obesity. Of these, 671 (84.4%) had the duodenal switch (DS) procedure. Longitudinal gastrectomy (LG) entails a greater curvature linear gastrectomy creating a gastric tube with a volume of 100 ml along the lesser curvature of the stomach. This procedure was performed for 21 patients (median age 50.5, median BMI 56). 9 patients were offered LG preoperatively because of their known high perioperative risks. 12 patients were initially planned for DS, but the procedure was limited to LG alone because of either unexpected intraoperative findings (n=9) or intraoperative hemodynamic instability (n=3). 5 patients developed complications, and there were no deaths. Results: 19 out of 21 patients were available for a median follow-up of 17.5 months (6.25-20.25). Median weight loss and median %EWL at 12 months were 44.5 kg and 45.1%, respectively. Estimated daily dietary volume at 1 year was 35% of preoperative values. Of 10 patients followed for ≥ 1 year, 4 of 10 achieved more than 50% EWL and 8 patients were taking less or were completely off medications for diabetes, hypertension and congestive heart failure. Weight loss plateaued at 1 year for the majority of patients. Conclusions: LG is a safe and effective option for high-risk morbidly obese patients. Weight reduction is accomplished by limitation of caloric intake. LG can be offered to high-risk morbidly obese patients as an interim procedure to help decrease perioperative risk before DS.     

Combining Laparoscopic Adjustable Gastric Banding and Biliopancreatic Diversion after Failed Bariatric Surgery

Background: A percentage of all types of bariatric surgery will fail. Our experience with failed biliopancreatic diversion (BPD) as a primary operation or revision operation for failed laparoscopic adjustable gastric banding (LAGB) convinced us that uncontrolled hunger is often the underlying cause. To control hunger after failed bariatric surgery,a novel approach combining LAGB with BPD-duodenal switch (DS) has been tried. Methods: Patients who had failed to lose weight after BPD or LAGB were considered in 2 groups. Group 1: patients who had failed LAGB underwent laparoscopic BPD-DS without sleeve gastrectomy, with the LAGB left in-situ. Group 2: patients who had failed primary (subgroup 2a) or revision (subgroup 2b) BPD had a LAGB placed with no other revision of their surgery. Results: 11 patients have undergone this form of revision surgery with little morbidity. Mean age at the original operation was 45 years, mean (range) BMI was 45.3 (38-62) kg/m². After the reoperation, at 3 months (9 patients) mean BMI was 30 kg/m² and at 6 months (4 patients) mean BMI was 27 kg/m². Conclusion: In this small study, combination surgery was safe and effective for failed BPD or LAGB. LAGB failure may be best managed with DS malabsorption without gastric resection.