生长抑素联合奥美拉唑治疗上消化道出血的临床分析

目的：探讨生长抑素联合奥美拉唑治疗上消化道出血的临床效果。方法整群选取该院2013年1月＿2016年5月期间收治的79例上消化道出血患者,将其随机分为研究组(40例﹚和对照组(39例﹚,研究组采取生长抑素联合奥美拉唑治疗,对照组单纯采取奥美拉唑治疗,比较两组止血时间、住院时间等。结果研究组平均止血时间(12.9±5.3﹚h、住院时间(10.4±2.2﹚d与对照组比较差异有统计学意义,P﹤0.05;研究组总有效率90.0%、再出血率12.5%与对照组比较差异有统计学意义,P﹤0.05。结论生长抑素联合奥美拉唑治疗上消化道出血效果确切,优于单纯使用奥美拉唑效果,值得临床推广。     

国产生长抑素联合前列地尔治疗高脂血症性急性胰腺炎临床观察

目的：探讨国产生长抑素联合前列地尔治疗高脂血症性急性胰腺炎的疗效及安全性。方法选取2012年5月至2015年5月于我院消化内科治疗的120例高脂血症性急性胰腺炎患者,按随机数表法分为对照组和观察组各60例。两组患者均给予常规治疗,对照组患者在此基础上给予前列地尔注射液10μg加生理盐水20 mL静脉注射;观察组患者在对照组治疗的基础上给予注射用国产生长抑素0.25 mg加入5%葡萄糖注射液250 mL中静脉滴注,疗程均为两周。比较两组患者治疗后的血清甘油三脂(TG)、C反应蛋白(CRP)、前白蛋白(PA)、血液流变学、血尿淀粉酶(AMS)指标;记录两组患者腹痛持续时间、腹膜炎体征消失时间、胃肠功能恢复时间、血淀粉酶恢复正常时间及住院时间,比较两组患者的临床疗效、并发症和不良反应发生率。结果观察组患者的治疗总有效率为96.7%(58/60),明显高于对照组的81.7%(49/60),差异有统计学意义(P<0.05);治疗后,观察组患者的血清TG、CRP、PA及各种血液流变学指标均显著优于对照组,差异均有统计学意义(P<0.05),而血、尿AMS水平与对照组比较差异均无统计学意义(P>0.05);观察组腹痛持续时间、腹膜炎体征消失时间、胃肠功能恢复时间、血淀粉酶恢复正常时间及住院时间分别为(7.3±4.3) d、(10.3±5.8) d、(4.3±1.1) d、(6.1±5.2) d、(17.4±9.5) d,均明显低于对照组的(9.3±5.3) d、(13.7±6.4) d、(7.1±1.8) d、(7.7±6.0) d、(24.4±10.8) d,差异均有统计学意义(P<0.05);观察组患者并发症发生率(6.7%)及不良反应发生率(3.3%)均显著低于对照组的30.0%和15.0%,差异均有统计学意义(P<0.05)。结论国产生长抑素联合前列地尔治疗高脂血症性急性胰腺炎疗效显著,其能够显著提高治愈率,缩短病程,且安全性较好。     

生长抑素联合前列地尔对重症急性胰腺炎患者的疗效及对TNF-αIL-6的影响

目的:研究生长抑素联合前列地尔对急诊重症急性胰腺炎( SAP )患者的疗效及对肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的影响. 方法:选择2012年6月至2015年5月接受治疗的SAP 患者96例实施研究,根据数字随机法分成观察组以及对照组两组,每组各有48例患者. 两组均予以常规禁食、胃肠减压以及抗生素等对症支持性治疗. 对照组增用生长抑素,观察组在对照组基础上增用前列地尔,治疗2 周后比较两组不同治疗方式的疗效,两组症状体征相关指标,内毒素、TNF-α及IL-6水平,以及药物不良反应. 结果:观察组经过治疗后的总有效率为95.83%,较对照组的81.25%显著更高( P<0.05). 观察组的腹痛缓解所需时间、肠功能恢复所需时间、血淀粉酶恢复所需时间以及ICU住院时间均分别少于对照组( P<0.05). 两组治疗前的内毒素、TNF-α及IL-6水平无统计学差异. 观察组治疗后的内毒素、TNF-α及IL-6水平均分别显著低于对照组( P<0.05). 两组不良反应比较,差异无统计学意义. 结论:利用前列地尔以及生长抑素对SAP 患者实施联合治疗,疗效较好,能够加速患者症状恢复,还可减少炎性介质的释放,安全性较高,值得退广应用.     

Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.     

Hemodynamic effects of somatostatin in insulin-dependent diabetic subjects

Summary The aim of the present study was to evaluate possible hemodynamic effects of somatostatin in insulin-dependent diabetic subjects. For this purpose, 7 insulin-requiring juvenile-onset diabetics were submitted to a short-term infusion of cyclic somatostatin (250 μg/h, over 2 h) or saline in randomized order. Somatostatin infusion resulted in a progressive and significant decrease in heart rate, stroke volume, cardiac index and velocity circumferential fiber; on the other hand, left ventricular ejection time was augmented by somatostatin. None of these effects was seen in the saline control study. We conclude that somatostatin exerts a negative inotropic effect in insulin-dependent diabetes.     

Basal and tolbutamide-induced plasma somatostatin in healthy subjects and in patients with diabetes and impaired glucose tolerance

Peripheral levels of basal and tolbutamide-induced somatostatin have been measured in patients with diabetes or impaired glucose tolerance (IGT) and compared with those in normal individuals. Basal somatostatin was significantly higher in patients with Type 1 diabetes than in age-matched control subjects. This increase was most pronounced at diagnosis, and appeared to be related to metabolic control in insulin-treated patients. No increase was noted in patients with Type 2 diabetes or with IGT. Intravenous bolus injection of tolbutamide enhanced peripheral somatostatin levels in healthy volunteers in a biphasic manner. Patients with IGT also exhibited a biphasic response but the amplitude of the first phase was higher. No secretory response was detected in 27/29 Type 1 diabetic patients at diagnosis; a somatostatin response to tolbutamide became detectable again in Type 1 patients with normalization of their basal somatostatin levels but was then paradoxically related to poor blood glucose control. In Type 2 diabetes, basal somatostatin levels were similar to age-matched control subjects, but decreased upon intravenous tolbutamide administration.     

A “false positive” octreoscan in ileal Crohn’s disease

We present a case report of a patient with a suspicious ileal carcinoid tumour. Clinical examination as well as computer tomograghy （CT） scan suggested a tumour. Octeotride scan showed uptake in the same bowel loop reported as pathological in CT. The patient underwent surgery and biopsy which reported Crohn’s disease （CD）. The interest in the case is due to the fact that this is, to the best of our knowledge, the second report of Crohn’sdisease as a cause of false positive octeotride scan. Unfortunately, no somatostatin recptors could be found in the sample, so further studies should be performed.     

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm², respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm² in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.     

Effects of somatostatin on acute pancreatitis induced in rats by injection of taurocholate and trypsin into a temporarily closed duodenal loop

Summary The effect of somatostatin on the course and severity of experimental pancreatitis was tested. Acute pancreatitis was induced in 210 Sprague-Dawely rats by injecting a 4.3% sodium taurocholate solution, saturated with trypsin, into a temporarily closed duodenal loop. Immediately after the end of the surgical procedure somatostatin or, alternatively, normal saline were administered as a bolus followed by continuous subcutaneous infusion for 9 h. Ninety rats (30 untreated, 30 saline-treated and 30 somatostatin-treated) were sacrificed 10 h after the induction of pancreatitis to assess the histologic severity of pancreatic lesions, the amount of peritoneal exudate and the circulating levels of amylase. In another 120 rats (40 untreated, 40 saline-treated and 40 drug-treated) the mortality rate was evaluated so that the histologic examination of the pancreas followed spontaneous death. In sacrificed animals somatostatin treatment lowered serum amylase levels and definitely improved pancreatic histopathology (edema, leucocyte infiltration and necrosis). The drug prevented the occurrence of severe necrosis in all treated animals. Somatostatin did not affect the mortality rate of pancreatitic rats (70%) although post-mortem histologic examination revealed significantly less pancreatic histopathology in drug-treated rats than in their controls.     

Polykystose rénale autosomique dominante : le traitement est-il pour demain ?

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent Mendelian inherited disorder. It covers 6.1% of incident ESRD patients in France in 2011. Long left untreated, this disease will soon benefit from targeted therapies currently under evaluation. Several molecules have already reached the stage of clinical trials: the evaluation of mTOR inhibitors yielded deceiving results and, more recently, 2 different molecules demonstrated a slight impact on the progression of total kidney volume (TKV): tolvaptan, vasopressin receptor-V2 inhibitor and somatostatin analogues; both of these molecules acting throughout the decrease of intracellular AMPc. The purpose of this review is to briefly describe the signaling pathways involved, then to present both the published and ongoing clinical trials and the promising molecules evaluated in murine models.