15The effect of Lower Esophageal Sphincter (LES) electrical stimulation on LES pressure

Background: Electrical stimulation (ES) of the stomach has been shown to modulate LESP. Electrical stimulation, using neural high frequency stimulation (NGES) can induce contractions of the smooth muscle of the gut. The purpose of this study was to determine if electrical stimulation of the LES can affect LESP. Methods: Four female hound dogs, weight: 20–25 kg, underwent an esophagostomy that allowed the introduction of a sleeve manometry catheter into the esophagus. They were also implanted with a pair of electrodes along the longitudinal axis of the LES. After 3 weeks of recovery, they underwent esophageal manometry recording during control and ES, performed randomly on separate days, using 4 different stimulations: 1‐Low frequency: freq: 6 cycles/min, pulse: 350 milisec, amp: 5 mAmp; 2 High‐frequency: freq: 50 Hz, pulse: 1 milisec, amp: 5 mAmp; 3‐ NGES: freq: 50 Hz, pulse:20 milisec, amp:10 volts; 4‐ High‐frequency, circular: freq: 20 Hz, pulse:1 milisec, amp:5 mAmp. All recordings were performed 1 hour after consumption of 3 ounces of canned dog food, to prevent fluctuations in LESP and under mild sedation (acepromazine 0.5 mg kg^­1). Tests consisted, during ES days, of 3 periods of 20 minutes each: control , stimulation and post stimulation. The effect of NGES was also tested under anesthesia and following administration of L‐NAME 50 mg kg^­1 IV. and also atropine 0.05 mg kg^­1 IV. Analysis: area under the curve (AUC) and pressure were compared among the 3 periods. Data shown as mean ± SD, ANOVA and t‐test, p < 0.05. Results: Sustained increase in LESP was observed during low frequency stimulation, 32.1 ± 12.8 vs. 42.4 ± 18.0 vs. 50.1 ± 23.6, control vs. stimulation vs. post stimulation respectively, p = 0.013. AUC also significantly increased during and after stimulation, 39,320.3 ± 15,722 vs. 51,294 ± 21,826 vs. 59,823.6 ± 28,198.4 mmHgxsec, control vs. stimulation vs. post stimulation respectively, p = 0.01. There was no significant change with other types of ES. NGES induced an initial rise in LESP followed within few seconds by relaxation with slow resumption of pressure over a 1 minute period. L‐NAME increased LESP and augmented the initial rise in LESP following NGES but markedly diminished or abolished the relaxation phase. Atropine lowered LESP and abolished the initial rise in LESP induced by NGES. Conclusions: Low frequency ES of the LES increases LESP in conscious dogs. NGES has dual effect on LESP: an initial stimulation, cholinergically mediated, followed by relaxation mediated by nitric oxide.     

Mesenterialarterienverschluss als seltene Komplikation bei Thrombangiitis obliterans

Mesenterialarterienverschlüsse sind eine seltene Komplikation der Thrombangiitis obliterans. Wir berichten über einen 30-j?hrigen Patienten mit einer Thrombangiitis obliterans und einem Mesenterialarterienverschluss als Komplikation dieser Erkrankung. Bei unklaren abdominellen Schmerzen wurden im Rahmen einer Laparoskopie ein Dünndarminfarkt und eine Minderperfusion der Leber bei dem Patienten diagnostiziert, sodass zun?chst eine Dünndarmteilresektion durchgeführt werden musste. Bei weiterhin bestehender Dünndarmisch?mie erfolgte dann eine Angiographie, die einen zentralen Verschluss des Truncus coeliacus und der A. mesenterica superior zeigte. Daraufhin wurde der Pat. relaparotomiert, die A. mesenterica superior embolektomiert, ein Venenbypass von der A. mesenterica superior zu beiden Leberarterien gelegt und eine erneute Dünndarmteilresektion durchgeführt. Nach initial unauff?lligem Verlauf und Entlassung wurde der Patient bei erneuter abdomineller Symptomatik 3 Wochen sp?ter wieder station?r aufgenommen und aufgrund eines akuten Verschlusses der A. colica dextra eine Hemikolektomie rechts durchgeführt. Seit einem Jahr ist bei dem Patienten keine abdominelle Symptomatik im Rahmen seiner Erkrankung mehr aufgetreten.     

Safety trial with the 5HT1B/1D agonist avitriptan (BMS-180048) in patients with migraine who have experienced pressure, tightness, and/or pain in the chest, neck, and/or throat following sumatriptan

We investigate whether symptoms of pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of the 5HT_1B/1D agonist avitriptan were associated with objective impairment of the myocardial function on 12-lead electrocardiogram (ECG), continuous ECG (Holter) monitoring, and echocardiography. Migraine sufferers who in two-thirds of alt attacks treated with sumatriptan had experienced chest/throat/neck symptoms were chosen for study. Baseline measures included vital signs, a 12-lead ECG and an echocardiogram. Patients ( n =51) who had no clinically significant abnormality at baseline received a high dose (150 mg) of avitriptan orally outside of a migraine attack. If pressure, tightness, and/or pain in the chest, neck, and/or throat occurred, an ECG was obtained, and a repeat echocardiogram was done while the symptoms were present in order to monitor for impairment of myocardial function. If symptoms of these types did not occur within 60 min after administration of the study drug, a second echocardiogram was obtained. Forty-five patients (88%) reported at least one adverse event and 23 (45%) experienced pressure, tightness, and/or pain in the chest, neck, and/or throat after administration of avitriptan. No clinically significant myocardial abnormalities were observed in any patient, even in those who had experienced the targeted symptoms. No other serious adverse event occurred. We concluded that the typical 5HT_1B/1D agonist-induced chest/throat/neck symptoms are most unlikely to be of cardiovascular origin.     

Efficacy of confrontational counselling for smoking cessation in smokers with previously undiagnosed mild to moderate airflow limitation: study protocol of a randomized controlled trial

Background  

The use of spirometry for early detection of chronic obstructive pulmonary disease (COPD) is still an issue of debate, particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation. We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed "confrontational counselling"; a patient-centred approach which involves specific communication skills and elements of cognitive therapy. An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions. The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation.     

Liver transplantation in malignant disease

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.     

女性护理专业学生心理健康相关因素分析

目的:分析护理专业学生心理健康的影响因素。方法:于2005-12-01/15按整群抽样法抽取西安市高校在读的护理专业学生515名作为被调查对象。症状自评量表总分≥187为高分组,总分≤116为低分组。高分组与低分组配比的条件是均为女性,年龄相差不超过3岁。采用症状自评量表、简易应对方式问卷、自尊量表、护理专业学生相关状况调查表进行问卷调查。对调查变量进行单因素和多因素Logistic回归分析。结果:共发放问卷515份,其中2名学生生病未填写调查表,应答率为99.6%。调查中有效问卷共507份,有效率为98.8%。症状自评量表总分高分组与低分组学生各100名。①护理专业学生心理健康相关个人因素(计量变量)单因素分析结果:高分组积极应对、自尊水平得分明显低于低分组(20.47±5.02,22.15±6.02;25.91±3.60,30.96±3.25),差异有显著性意义(P<0.05,P<0.01)。高分组消极应对得分明显高于低分组(12.57±4.08,8.00±4.12),差异有显著性意义(P<0.01)。②护理专业学生心理健康相关个人因素(二分类变量)单因素分析结果表明,高分组与低分组比较差异有显著性的因素有独生子女、远离家人、孤独、学习压力大、担心拿不到学位、自我实现需要的满足、经常被人误会、受人歧视、失恋、有知心朋友、无处倾诉苦恼、睡眠型态紊乱、近1年来本人健康改变、适应新环境、经常参加体育活动、担心毕业分配、现有最担心的事情。③多因素分析显示,学习压力大(OR=10.017)、近1年来本人健康改变(OR=4.384)为护理专业学生心理健康状况不良的独立危险因素,而自我实现需要的满足(OR=0.037)、高水平自尊(OR=0.357)是保护因素。结论:护理专业学生心理健康状况与教育、成长、社会环境等多方面因素相关,其心理健康干预需考虑学生的个人因素有针对性地进行。     

Pharmacological characterization of CXC chemokine receptor 3 ligands and a small molecule antagonist

The CXC chemokine receptor 3 (CXCR3) is predominantly expressed on T helper type 1 (Th1) cells that are involved in inflammatory diseases. The three CXCR3 ligands CXCL9, CXCL10, and CXCL11 are produced at sites of inflammation and elicit migration of pathological Th1 cells. Here, we are the first to characterize the pharmacological potencies and specificity of a CXCR3 antagonist, N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide (NBI-74330), from the T487 small molecule series. NBI-74330 demonstrated potent inhibition of [(125)I]CXCL10 and [(125)I]CXCL11 specific binding (K(i) of 1.5 and 3.2 nM, respectively) and of functional responses mediated by CXCR3, such as ligand-induced guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding, calcium mobilization, and cellular chemotaxis (IC(50) of 7 to 18 nM). NBI-74330 was selective for CXCR3 because it showed no significant inhibition of chemotactic responses to other chemokines and did not inhibit radioligand binding to a panel of nonchemokine G-protein coupled receptors. There was a striking difference in potencies among the three CXCR3 ligands, with CXCL11 > CXCL10 > CXCL9. A comparison of the rank order of K(i) values with the rank order of monocyte production levels of these three ligands revealed a precise inverse correlation, suggesting that the weaker receptor affinities of CXCL9 and CXCL10 were physiologically compensated for by an elevated expression, perhaps to maintain effectiveness of each ligand under physiological conditions.     

Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo

OBJECTIVE: To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 (30 microg/ml zinc) in comparison with those of NPH insulin and placebo. RESEARCH DESIGN AND METHODS: In this single-center double-blind euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 +/- 4 years, BMI 22.2 +/- 1.8 kg/m2) received single subcutaneous injections of 0.4 U/kg body wt of HOE901, NPH insulin, or placebo on 3 study days in a randomized order. The necessary glucose infusion rates (GIRs) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration. RESULTS: The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin (GIRmax 5.3 +/- 1.1 vs. 7.7 +/- 1.3 mg x kg(-1) x min(-1)) (P < 0.05); after an initial rise, metabolic activity was rather constant over the study period. This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection (area under the curve from 0 to 4 h [AUC(0-4 h)] 1.02 +/- 0.34 vs. 1.48 +/- 0.34 g/kg) (P < 0.001) with HOE901, as compared with NPH insulin. In this single-dose study, the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin (AUC(0-30 h) 7.93 +/- 1.82 vs. 9.24 +/- 1.29 g/kg) (P < 0.05). CONCLUSIONS: This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin, from which a better substitution of basal insulin requirements may follow.     

Relief of reflux symptoms after endoscopic gastroplication may be associated with reduced esophageal Acid sensitivity: a pilot study

BACKGROUND AND STUDY AIMS: Although the new endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) lead to marked clinical benefit, the underlying mechanism of this is unknown. MATERIALS AND METHODS: In this prospective study, the effect of endoscopic gastroplication was investigated in six patients with GERD, who were assessed before and 4 weeks after treatment. The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI) consumption, reflux esophagitis, acid exposure, esophageal motility, lower esophageal sphincter pressure (LESP), and gastric emptying was measured. Esophageal acid sensitivity before and after treatment was investigated using a standardized acid provocation test, and compared with that of six age- and sex-matched healthy controls. RESULTS: Significant clinical benefit and discontinuation of PPI consumption after gastroplication was seen. Among the objectively measured parameters, only acid exposure was significantly reduced and gastric emptying significantly delayed. However, acid exposure remained pathologically high. Esophageal acid sensitivity was significantly reduced. The induction of heartburn and/or pain was abolished in four patients after gastroplication. In two patients the intensity of heartburn/pain was significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain significantly prolonged by 40% or 100%. CONCLUSION: These preliminary data suggest that the decrease of esophageal sensitivity to acid after endoscopic gastroplication is part of the mechanism responsible for the reduction of reflux symptoms.