Differences in prolonged ischemia length using ischemic preconditioning in the rabbit heart. Tolerable limitation time for surgically induced myocardial ischemia during normothermic cardiac operation

BACKGROUND: To determine the effect of the tolerable limitation time of prolonged ischemia after ischemic preconditioning on postischemic functional recovery and infarct size reduction in the rabbit heart. METHODS: White rabbits (n=30) were used for Langendorff perfusion. Control hearts were perfused at 37 degrees C for 180 min; 30 min global ischemia hearts (30GI) received 30 min global ischemia and 120 min reperfusion; IPC+30GI hearts received 5 min zero flow global ischemia and 5 min reperfusion prior to 30 min global ischemia; 20 min global ischemia hearts (20GI) received 20 min global ischemia and 120 min reperfusion; IPC+20GI hearts received 5 min zero flow global ischemia and 5 min reperfusion prior to 20 min global ischemia. RESULTS: Infarct size in the 30GI hearts was 33.5+/-4.0% and 1.7+/-0.5% in the control hearts. The 20GI hearts and IPC+30GI hearts decreased infarct size, as compared with the 30GI hearts (13.0+/-1.8% and 16.6+/-1.7%, respectively; p<0.001, 20GI vs 30GI; p<0.01, IPC+30GI vs 30GI; p>0.05, 20GI vs IPC+30GI) but did not enhance postischemic functional recovery. The IPC+20GI hearts (3.5+/-0.6%) significantly decreased infarct size as compared with the 20GI hearts (p<0.05, IPC+20GI vs 20GI), and there was no significant difference between the IPC+20GI and the control hearts (p>0.05), but the IPC+20GI hearts did not enhance postischemic functional recovery. CONCLUSIONS: A 20 min ischemia may be the tolerable limitation time of prolonged ischemia after ischemic preconditioning in an isolated rabbit heart model.     

Simultaneous upper and lower endoscopic biopsy in the diagnosis of intestinal graft-versus-host disease

Graft-versus-host disease in the upper gastrointestinal tract presents with anorexia, vomiting, and abdominal discomfort. Because these symptoms are not specific, we have proposed that a diagnosis of upper GI GVHD requires histologic confirmation. However, the utility of upper endoscopy in the diagnosis of upper GI GVHD has not been examined. We report a retrospective analysis of 77 allogeneic bone marrow transplantation recipients who received simultaneous upper and lower GI tract biopsies. Upper GI GVHD was found in 44% of patients, of whom 59% also had a positive lower GI tract biopsy (P less than 0.001). Thirty-five percent of the patients with no clinical evidence of lower GI tract GVHD had symptomatic upper GI GVHD confirmed histologically. Patients with and without upper GI GVHD had no significant difference in their clinical symptoms or in their endoscopic findings. We found an association between upper GI and skin GVHD greater than stage I (P = 0.05), a trend to concordance between upper GI GVHD and clinical GVHD in the lower GI tract (P = 0.08), and with the overall clinical GVHD grade (P = 0.08) but no association with clinical liver involvement. Of these 77 patients, 16% had their treatment for acute GVHD changed to include systemic immunosuppression as a result of the upper GI endoscopic biopsy. In addition, 71% had other enteric pathology identified that required specific therapy. These data suggest that upper GI GVHD cannot be diagnosed accurately from its clinical presentation nor inferred from lower GI symptoms or from extraintestinal GVHD. Upper GI endoscopy with biopsy is an important tool in the diagnosis of intestinal GVHD.     

Extra-gastrointestinal stromal tumor of the pancreas: case report and a review of the literature

Gastrointestinal (GI) stromal tumors are mesenchymal tumors that arise from the GI tract. In rare cases, these tumors are found in intra-abdominal sites unrelated to the GI tract and are immunohistochemically similar to their GI tract counterparts. Primary pancreatic GI stromal tumors are very rare, with only 4 previous cases reported.     

Gastrointestinal growth factors and neoplasia

Gastrointestinal (GI) hormones are chemical messengers that have been recognized for over a century as regulatory factors for normal physiologic functions in the GI tract and pancreas, including absorption, secretion, motility, and digestion. These hormones traditionally act in a true endocrine fashion with release from a distant site to regulate physiologic functions of specific target organs. In general, GI hormones bind to their G-protein-coupled receptors (GPCRs) to produce their endocrine effects. In addition to effects on physiologic functions of the GI tract and pancreas, selected GI hormones can act in an endocrine, paracrine, and/or autocrine fashion to stimulate the proliferation of normal and neoplastic GI tissues as well as non-GI tissues. This review will focus on effects of GI hormones on neoplastic tissues concentrating on the hormones that have been best characterized for these effects.     

Gastrointestinal symptoms in intensive care patients

Background: Gastrointestinal (GI) problems are not uniformly assessed in intensive care unit (ICU) patients and respective data in available literature are insufficient. We aimed to describe the prevalence, risk factors and importance of different GI symptoms. Methods: We prospectively studied all patients hospitalized to the General ICU of Tartu University Hospital in 2004–2007. Results: Of 1374 patients, 62 were excluded due to missing data. Seven hundred and seventy‐five (59.1%) patients had at least one GI symptom at least during 1 day of their stay, while 475 (36.2%) suffered from more than one symptom. Absent or abnormal bowel sounds were documented in 542 patients (41.3%), vomiting/regurgitation in 501 (38.2%), high gastric aspirate volume in 298 (22.7%), diarrhoea in 184 (14.0%), bowel distension in 139 (10.6%) and GI bleeding in 97 (7.4%) patients during their ICU stay. Absent or abnormal bowel sounds and GI bleeding were associated with significantly higher mortality. The number of simultaneous GI symptoms was an independent risk factor for ICU mortality. The ICU length of stay and mortality of patients who had two or more GI symptoms simultaneously were significantly higher than in patients with a maximum of one GI symptom. Conclusion: GI symptoms occur frequently in ICU patients. Absence of bowel sounds and GI bleeding are associated with impaired outcome. Prevalence of GI symptoms at the first day in ICU predicts the mortality of the patients.     

Ultrasonographic evaluation of gastrointestinal graft‐versus‐host disease after hematopoietic stem cell transplantation

Gastrointestinal graft‐versus‐host disease (GI‐GVHD) is a major and life‐threatening complication of hematopoietic stem cell transplantation (HSCT). This study evaluated the efficacy of ultrasonography (US) for assessing and monitoring GI‐GVHD. GI tract was evaluated by US in 81 patients. US findings were positive in 43 patients, including 11 false positive, and negative in 38 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for the diagnosis of GI‐GVHD were 100%, 78%, 74%, 100%, and 86%, respectively. Diffuse wall thickening of the ileum was the most frequent finding in patients with GI‐GVHD. Severity of GI‐GVHD was correlated with the thickness of internal low echoic layer of the wall, the echogenicity of mesenteric fat tissue, and the intensity of Doppler signaling. We classified US findings of GI‐GVHD into four US grades. There was a significant correlation between clinical stage of GI‐GVHD and the US grade. These ultrasonographic abnormalities were improved with clinical improvement of GI‐GVHD upon treatment. Thus, US is an effective and efficient non‐invasive means of identifying the extent and severity of GI‐GVHD and monitoring response to treatment.     

Clinicians underestimate gastrointestinal symptoms and overestimate quality of life in renal transplant recipients: a multinational survey of nephrologists

Gastrointestinal (GI) symptoms are common in renal transplant recipients and are associated with impaired health-related quality of life (HRQoL). We investigated clinician attitudes to GI symptoms and HRQoL in these patients by surveying 145 nephrologists from Sweden, Denmark, Finland, and Norway. In total, 79 clinicians responded. They estimated that 20% of their patients experienced GI discomfort and that 36% had impaired HRQoL. We previously conducted a survey of the renal transplant recipients treated by these clinicians, in which 92% reported troublesome GI symptoms and 53% had impaired HRQoL compared with the general population. Nephrologists were more likely to manage GI symptoms by reducing immunosuppressant dose (87%) than by switching medication to one with fewer GI side effects (66%). We conclude that clinicians appear to underestimate the prevalence of GI symptoms and impaired HRQoL. Improving patient-clinician communication could lead to more informed management, resulting in better HRQoL and increased graft survival.     

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目的 总结肝脏与胃肠道同时存在甩块的处理原则。方法 分析１２例肝脏与胃肠道同时有肿块而术中或术后病理检查证实并非癌肿转移关系者的临床资料。结果 ７例为同时性双重癌,３例为肝脏癌肿并胃肠道良性疾病,１例为结肠癌伴套迭而肝脏病灶来自胰腺囊实性氏度恶性）,另１例肝脏与胃肠道均为良性疾病。结论 肝脏与胃肠道同时存在的肿块并不一定是癌肿转移,可能为同时性双重癌或伴发良性肿物,非团长 变的治疗与转移性癌截然不     

Interventional radiological treatment of gastrointestinal bleeding

Summary   Background: Gastrointestinal (GI) bleeding is divided into upper and lower GI bleeding. The most common reasons for upper GI bleeding are gastric and duodenal ulcers. Lower GI bleeding is located in the intestine below the ligament of Treitz. In this review article the possibilities for interventional radiological treatment of gastrointestinal bleeding will be discussed. Methods: Interventional treatment in form of embolization of arterial branches of the celiac trunc is indicated if endoscopic approaches fail to stop the bleeding. Localization and treatment of lower GI bleeding is more difficult and technically more demanding. Embolization of mesenteric branches may be effective to stop bleeding but carries the risk of inducing bowl ischemia. Sometimes surgical exploration can be necessary after embolization. However, especially in severe bleeding, embolization may help to stabilize the patient before major surgery. If the bleeding source can not be identified, intraarterial infusion of vasoactive drugs, like vasopressin, may be effective. Results: In upper GI bleeding, hemostasis can be achieved by transarterial embolization in up to 91 %. In lower GI bleeding the success rate is less well defined, since there are no larger series available in the current literature. In all embolization procedures, the risk of ischemic bowl damage has to be considered. This complication occurs more often in embolization after in lower GI bleeding. Conclusions: Transarterial embolization offers an efficient treatment of upper and lower GI bleeding. It should be used for upper GI bleeding when endoscopic hemostasis is not so successful. In lower GI bleeding transarterial embolization often has the character of a temporizing procedure before surgery.      

Impact of mycophenolate mofetil (MMF)-related gastrointestinal complications and MMF dose alterations on transplant outcomes and healthcare costs in renal transplant recipients

Mycophenolate mofetil (MMF), a mycophenolic acid prodrug, is a highly effective adjunct immunosuppressive agent in transplant therapy. Although MMF is generally well tolerated, optimal therapy may be limited by adverse effects, in particular gastrointestinal (GI) toxicity, which has been reported to occur in up to 45% of MMF-treated patients. MMF dose changes resulting from these adverse events may lead to sub-therapeutic dosing and impaired clinical outcomes. This retrospective study analyzed clinical records from 772 renal transplant patients from 10 US transplant centers who were initiated on MMF. The analysis revealed that 49.7% (n = 382) of patients experienced at least one GI complication within the first 6 months post-transplant, with 66.8% (n = 255) of these having multiple GI complications. Of the patients with GI complications, 39.0% experienced MMF dose adjustments or discontinuation of MMF therapy. Patients with GI complications who experienced MMF dose adjustments/discontinuation had a significantly increased incidence of acute rejections compared with patients without GI complications (30.2% vs. 19.4%; p = 0.005). Mean treatment costs were higher in patients with GI complications than in those with no GI complications, particularly in those who experienced MMF dose adjustments/discontinuation (p = 0.0001). The mean incremental cost for patients experiencing GI complications was US$3700 per patient during the 6 months post-transplant (p < 0.001), which was mainly attributable to hospitalization costs. In summary, GI complications and MMF dose adjustments/discontinuations are associated with a significant negative impact on transplant outcomes and markedly increase short-term treatment costs.     

Epidemiology of RHDV2 (Lagovirus europaeus/GI.2) in free‐living wild European rabbits in Portugal

As the detection of the first outbreak of a novel aetiological agent of rabbit haemorrhagic disease commonly called RHDV 2 or RHDV b (Lagovirus europaeus /GI .2, henceforth GI .2) in France in 2010, the virus rapidly spread throughout continental Europe and nearby islands such as Great Britain, Sardinia, Sicily, the Azores and the Canary Islands among others. The outbreaks of this new lagovirus cause important economic losses in rabbitries, and ecological disruptions by affecting the conservation of rabbit‐sensitive top predators. We analysed 550 rabbit carcasses collected in the field between May 2013 and March 2016, to investigate the epidemiology of GI .2 in free‐living populations and to perform a comparative analysis with the epidemiology of classical rabbit haemorrhagic disease virus forms (RHDV , henceforth GI .1) in Portugal. Rabbits were sexed, aged and liver and blood samples were collected for subsequent RHDV screening and serology. A total of 172 samples were PCR‐positive to GI .2, whereas GI .1 strains were not detected in any of the samples. The outbreaks of GI .2 revealed a marked seasonality, with peaks during the breeding season (November‐May). We also found that approximately, one‐third of free‐ranging European rabbits in Portugal have seroconverted to GI .2. We demonstrate that the GI .2 lagovirus is currently widespread in wild populations in Portugal and is affecting a high proportion of adults and juveniles. Therefore, ongoing monitoring and surveillance are required to assess the effects of GI .2 on wild rabbit populations, its evolution, and to guide management actions aimed at mitigating the impacts of rabbit declines in the ecosystem and in rural economies.     

Gastrointestinal complications in liver transplant recipients: MITOS study

INTRODUCTION: Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. OBJECTIVE: The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. PATIENTS AND METHODS: This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. RESULTS: The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. CONCLUSIONS: The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.     

Ghrelin Agonist TZP-101/Ulimorelin Accelerates Gastrointestinal Recovery Independently of Opioid Use and Surgery Type: Covariate Analysis of Phase 2 Data

Background  

Delayed recovery of gastrointestinal (GI) motility is a common complication following surgery. TZP-101/ulimorelin is a macrocyclic peptidomimetic ghrelin receptor agonist with GI promotility effects that significantly accelerates time to recovery of GI motility compared to placebo following partial colectomy. It is also well tolerated. The objectives of this analysis were to identify predictors of GI motility recovery in patients undergoing partial colectomy and to evaluate whether these factors affect ulimorelin acceleration of GI recovery.     

胃肠道脂肪瘤的诊断与治疗

目的总结胃肠道脂肪瘤的诊断与治疗经验。方法回顾性分析1993年至2007年间收治的34例胃肠道脂肪瘤的临床资料。结果胃肠道脂肪瘤的临床表现无特异性,可并发肠套叠或肠梗阻,超声内镜的诊断准确率为93.8%。本组有12例行内镜下脂肪瘤切除术,22例行开腹手术（局部切除术及胃或肠部分切除吻合术）,手术过程顺利,未出现并发症。28例（82.4%）获1-168个月随访,1例胃底多发的脂肪肉瘤于术后2年死于肿瘤转移,其余27例均无复发或转移,存活至今。结论超声内镜是诊断胃肠道脂肪瘤的有效方法,手术是治疗胃肠道脂肪瘤的常规手段,内镜下切除胃肠道脂肪瘤可行。     

Immunosuppressive drugs and the gastrointestinal tract in renal transplant patients

Gastrointestinal (GI) discomfort is common after renal transplantation and can be caused by the use of various immunosuppressive drugs. GI symptoms affect the quality of life, lead to an impaired graft survival and an increased mortality. Moreover, diseases and disturbances of the GI tract also affect the pharmacokinetics of immunosuppressive drugs. This review addresses the interaction between immunosuppressive agents and GI disorders.The GI tract is involved in the metabolism of several immunosuppressive drugs. Calcineurin inhibitors, mTor inhibitors, and corticosteroids are subjected to metabolism by the intestinal cytochrome P450 (CYP3A) and by the drug efflux pump ABCB1. Mycophenolate is partly metabolized in the stomach and intestine and undergoes enterohepatic recirculation. Gastrointestinal disturbances can lead to a modified exposure to immunosuppressive drugs. In the first and second part of this review, we focus on the role of the GI tract in the pharmacokinetics of the immunosuppressive drugs and how to adjust immunosuppressive therapy in patients with vomiting, need for tube feeding, delayed gastric emptying, intestinal resection, and diarrhea.In the third part, we review the GI adverse effects of the various immunosuppressive drugs, with special attention for diarrhea and dyspepsia.Finally, we discuss the effects of drugs used for relief of GI complaints on the exposure to immunosuppressive agents.     

Insights into the evolution of the new variant rabbit haemorrhagic disease virus (GI.2) and the identification of novel recombinant strains

Rabbit haemorrhagic disease (RHD ) is a viral disease that affects the European rabbit. RHD was detected in 1984 in China and rapidly disseminated worldwide causing a severe decline in wild rabbit populations. The aetiological agent, rabbit haemorrhagic disease virus (RHDV ), is an RNA virus of the family Caliciviridae , genus Lagovirus . Pathogenic (G1‐G6 or variants GI .1a‐GI .1d) and non‐pathogenic strains (GI .4) have been characterized. In 2010, a new variant of RHDV , RHDV 2/RHDV b/GI .2, was detected in France. GI .2 arrived to the Iberian Peninsula in 2011, and several recombination events were reported. Here, we sequenced full genomes of 19 samples collected in Portugal between 2014 and 2016. New GI .2 recombinant strains were detected, including triple recombinants. These recombinants possess a non‐structural protein p16 related to a non‐pathogenic strain. Evolutionary analyses were conducted on GI .2 VP 60 sequences. Estimated time to the most recent common ancestor (tMRCA ) suggests an emergence of GI .2 in July 2008, not distant from its first detection in 2010. This is the first study on GI .2 evolution and highlights the need of continued monitoring and characterization of complete genome sequences when studying lagoviruses’ evolution.     

心脏手术后消化道出血44例临床分析

目的探讨心脏手术后并发消化道出血的诊断、处理和相关危险因素。方法回顾性分析1991年1月至2003年10月间8317例成人心脏手术后的44例消化道出血患者的临床资料,采用多因素logistic回归分析方法分析死亡相关危险因素。结果消化道出血发生于术后2～11d,平均(6±3)d,病死率为23%(10/44)。上消化道出血者38例,其中保守治疗26例,死亡4例,与心脏手术后引起其他重要脏器损伤或心脏本身有关;行剖腹探查手术6例,死亡4例,其中1例死于败血症、3例死于多器官功能衰竭;胃镜下电灼或夹闭出血点止血6例,均存活。下消化道出血6例,其中2例行剖腹探查术中未发现出血点,后死于多器官功能衰竭。术后呼吸机依赖、急性肾功能不全、使用主动脉内球囊反搏和剖腹手术为消化道出血死亡危险因素。结论心脏手术后消化道出血病死率较高,对高危病例有必要采取预防措施;早期进行内窥镜下诊断、微创介入止血处理可取得较好的效果。     

Prevention of upper gastrointestinal bleeding in burn patients: a role for 'elemental' diet

In a retrospective study, the role of the elemental diet in preventing upper gastrointestinal (GI) bleeding was evaluated in 146 severely burned patients. The patients were divided into two groups. Group A consisted of 77 patients with 20% to 80% body-surface-area burns who received the usual diet. Group B consisted of 69 patients with similar-sized burns receiving Vivonex as the elemental diet. In group A, the incidence of upper GI bleeding was 44%, major upper GI bleeding was 30%, and two patients required surgery. The incidence of upper GI bleeding in group B was 20%, major upper GI bleeding was 3%, and no patients required surgery. Group A had 55% mortality, and group B, 38% mortality. Vivonex was associated with a noticeable decrease in major upper GI bleeding in severely burned patients, and unlike antacid and cimetidine therapy, contributed concomitantly to increased caloric intake.     

胃肠功能因素对骨科患者肠系膜上动脉综合征的影响

目的：探讨肠系膜上动脉综合征的发生机理，分析胃肠功能因素在该综合征中的作用。方法：联系骨科临床中常见的腹胀、便秘(胃肠功能紊乱)，观察19例非脊柱矫形病人发生的系膜上动脉综合征的发生、发展、治疗，分析其共同规律并研究其发生机理。结果：所有病例均发生于入院或术后1～2周，痊愈后无复发，此综合征因医疗干预时期不同及胃肠功能恢复速度不同而所需痊愈时间不同。结论：胃肠功能因素在系膜上动脉综合征的发生中起重要作用。该综合征是局部解剖因素及胃肠功能因素共同作用，并使胃肠通过功能进入恶性循环的结果，其治疗即是及时阻断此恶性循环，一般并不需手术治疗。