Sildenafil relieves symptoms and normalizes motility in patients with oesophageal spasm: a report of two cases

Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25-50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25-50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed.     

X-ray diffraction and electrochemical impedance spectroscopy study of zinc coated LiNi0.5Mn1.5O4 electrodes

Coating and doping with zinc have been used to modify LiNi_0.5Mn_1.5O₄ powders prepared at 700 and 800 °C. As previously found in the literature, surface treatment with zinc leads to a net improvement of the electrochemical performance of the 5-V electrode in lithium cells. X-ray diffraction reveals the occurrence of surface ZnO, which disappears after heating at 500 °C. This indicates that ZnO forms a coating, although zinc can also be incorporated in the LiNi_0.5Mn_1.5O₄ framework. The electrochemical oxidation of both bare LiNi_0.5Mn_1.5O₄ and zinc treated products has been followed by ex situ X-ray diffraction of charged electrodes. For both materials a decrease in the cubic unit cell parameter and the formation of two cubic phases during lithium extraction has been found. Lattice contraction is significantly larger in the sample modified with zinc. EIS measurements give direct evidence of the better stabilization of the electrode surface in the coated material.     

Validation of impedance cardiography measurements of cardiac output during limited exercise in heart transplant recipients

Abstract. Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients.     

Determination of diffusion coefficient of hydrogen in metals and their elastic modulus by generalised impedance

Transport of hydrogen in elastic metals has been analysed in terms of an impedance-like non-linear transfer function (TF). The equilibrium in a membrane specimen is perturbed by a sinusoidal signal of the concentration of hydrogen, of large amplitude, applied to one of its surfaces. The fundamental harmonics of periodically reproducible flux at the same surface is considered as a response. The TF is defined as the ratio of the signal to the response. The power of the said TF in determining the diffusion coefficient of hydrogen in a metal–hydrogen system and its bulk elastic modulus was analysed for the example of α-phase Pd–H and Pd₈₁Pt₁₉–H systems. It has been found that such a TF is suitable for determination of the above parameters. Also, the sensitivity of these estimates to the uncertainty of concentration of hydrogen in the metal, its partial molar volume and the thickness of the specimen has been explored.     

The nocturnal jejunal migrating motor complex: defining normal ranges by study of 51 healthy adult volunteers and meta-analysis

Interdigestive human small bowel motility is characterized by the migrating motor complex (MMC). The aims of this study were to: (i) establish the normal range of variables of the nocturnal jejunal MMC and (ii) incorporate these data in a subsequent meta-analysis. Eighty-one recordings were performed by prolonged (24 h) ambulatory manometry in 51 subjects in two centres. Quantitative analysis was undertaken of 419 Phase III and 332 Phase II episodes. Adjusted mean values of seven variables were calculated using a mixed-effects model. Meta-analysis of pooled published data to generate a reliable 95% reference range was also performed. Adjusted mean values and confidence intervals are presented for all seven variables. Intrasubject variances were large in comparison with intersubject. Meta-analysis of 19 studies (356 pooled patients) meeting inclusion criteria produced wide reference ranges. At least five such ranges are useful for the detection of abnormality in the individual. This is the largest study of normal volunteers presented to date, with ranges for many variables produced using appropriate statistical methodology. A model for definition of abnormality has been proposed. We recommend that these data may be used by investigators in this field as a complement to other existing indicators of small bowel dysmotility.     

腹泻型、便秘型肠易激综合征和功能性便秘患者的直肠肛管测压比较

目的研究腹泻型、便秘型IBS和功能性便秘患者直肠肛管测压参数的不同，并评价性别和年龄对各项参数的影响，方法腹泻型IBS(n=18)、便秘型IBS(n=14)、功能性便秘(n=30)和健康对照组(n=18)，通过定点牵拉法进行直肠肛管测压。结果腹泻型IBS、便秘型IBS、功能性便秘以及健康对照组直肠肛管测压各项压力参数基本无差异，但三组患者的诱发RAIR所需的最小气体容量均显著高于健康对照组，便秘型IBS和功能性便秘模拟排便时发生矛盾运动的百分比显著高于腹泻型IBS和健康对照组；便秘型IBS和功能性便秘组中，肛管上部和下部最大紧缩压力，以及模拟排便发生矛盾运动的百分比男性均高于女性；腹泻型IBS组内男性模拟排便发生矛盾运动的百分比高于女性；健康对照组内男性肛管下部静息压力和最大紧缩压力高于女性；各组20-50岁人群和50-80岁人群的各项压力参数无显著性差异，但功能性便秘组青年组诱发RAIR所需的最小气体容量低于老年组。结论腹泻型IBS、便秘型IBS和功能性便秘患者的直肠肛管测压各项压力参数无助于这三型功能性肠病的鉴别诊断。男性的直肠肛管测压的多项压力参数显著高于女性，男性更易出现模拟排便矛盾运动，年龄对直肠肛管测压各项参数无明显影响。     

Infusion manometry and detection of sphincteric function of crural diaphragm

The principles of infusion manometry in the measurement of lower esophageal sphincter (LES) pressure were laid down in the mid-1960s by L.D. Harris and his coworkers. Dodds and his colleagues were largely responsible for the improvements and advent of the low-compliance manometry. Using side-hole manometry, it is possible to detect accurate LES pressure that correlates with the strength of the antireflux barrier. The LES pressure as measured by the side-hole manometry, shows respiration-induced pressure oscillations. These pressure oscillations were initially thought to be due to the influence of abdominal and thoracic pressures on the LES. However, it was later pointed out that these pressure oscillations were due to the relative motion of the point pressure sensor (side hole of the manometric catheter) and the LES during respiration. Recent studies suggest that active contraction of the crural diaphragm during inspiration is responsible for the pressure oscillations observed in the cat LES pressure tracings. The use of the sleeve device in the measurement of LES pressure during contraction of the diaphragm has been described recently. Using the principles of manometry and sleeve device, it is now possible to identify two lower esophageal sphincters: the smooth muscle LES, traditionally known as the LES, and crural diaphragm, which we have referred to as the external lower esophageal sphincter. The purpose of the following paper is to summarize the general principles of the infusion manometry in the measurement of intraluminal pressure, specifically the LES pressure. The recently developed technique of detection of the sphincteric function of the crural diaphragm by the sleeve device will be discussed. In the last paragraph the limitations of manometry in detection of the muscular contractile activity are described.     

Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.     

The effects of acute exercise on colonie motility

Abstract Changes in colonic motor activity during aerobic exercise were investigated in ten regularly exercising volunteers (five males and five females) aged 27–70 years. Motility was recorded with a catheter containing three solid-state pressure transducers spaced 5 cm apart. The motility catheter was advanced 40–50 cm from the anal verge by flexible sigmoidoscope without anesthesia at least 60 min prior to testing. Manometric recordings were made from the colon during a 1-h pre-exercise rest period, 1 h of jogging at 70–80% maximum heart rate, and 1-h post-exercise rest period. The dominant frequency of contractile activity in the colon shifted from 1–4 cpm during rest, to 4–9 cpm with the onset of exercise. Activity also shifted from sporadic, isolated contractions to regular, propagated contractions in six of ten subjects, five of whom reported a history of runner's diarrhoea. The dominant frequency returned to 1–4 cpm during the post-exercise period. These changes in distal colonie motility may account for the diarrhoea which some subjects experience during intense, acute exercise.     

Influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis

This study was designed to determine the influence of ileal pouch capacity and anal sphincteric function on the clinical outcome after ileal pouch-anal anastomosis. A total of 24 patients who had undergone ileal pouch-anal anastomosis (J pouch) for ulcerative colitis were studied. The 24-hour stool frequency was found to be inversely correlated with the sensitivity threshold volume (STV), maximal tolerance volume (MTV), and distensibility, but was independent of the maximal resting pressure and maximal squeeze pressure. Patients experiencing nocturnal fecal incontinence had maximal resting pressures that were significantly lower than those of nocturnally continent patients. Among the patients with fecal incontinence, those with frequent soiling had lower resting pressures, STV, and distensibility than the patients with intermittent spotting. In addition, the STV in patients needing nocturnal evacuation were lower than those of patients who did not evacuate after falling asleep. The conclusions are as follows. Both stool frequency and the need for nocturnal pouch evacuation correlated directly with pouch volume. Anal incontinence was more common in patients with low internal sphincteric function. In addition, frequent and gross nocturnal incontinent patients demonstrate a worse function in both the anal sphincter and reservoir than those with intermittent spotting.