食管运动功能在重度反流性食管炎中的地位

目的　通过对重度反流性食管炎(RE)治愈前后食管体部运动功能的研究,了解食管体部运动功能在重度RE中的地位。方法　对70例胃食管反流病患者进行食管压力测定。从中筛选23例重度RE(内镜诊断为洛杉矶C和D级食管炎);且24h食管内pH监测证实为病理性酸反流;食管压力测定证实有食管体部运动障碍患者。给予兰索拉唑30mg/d治疗3~6个月至内镜下食管炎完全愈合后,再行食管压力测定,观察下食管括约肌静息压(LESP)及食管体部运动功能的变化。以湿咽成功率、食管远端收缩波幅和食管蠕动的传导速度作为食管体部运动功能的指标。结果　食管炎治愈前后,LESP[ (6 00±0 86 )mmHg比(5 10±0 87)mmHg, 1kPa=7 5mmHg, P=0 476],食管远端收缩波幅[ (34 1±4 1)mmHg比(37 2±4 0)mmHg,P=0 593]、湿咽成功率[ (33 5±6 5)%比(38 6±7 1 )%,P=0 592 ]比较差异均无统计学意义,其均值仍显著低于正常对照组。结论　治愈食管炎并不能提高LESP及改善食管体部的运动功能。食管体部运动功能障碍和酸反流是RE的重要发病机制,尤其是重度RE。     

Correlation of esophageal pH and motor abnormalities with endoscopic severity of reflux esophagitis

Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.     

Healing of severe reflux esophagitis with PPI does not improve esophageal dysmotility

Esophageal dysmotility is frequently associated with gastroesophageal reflux disease (GERD). The aim of this study was to investigate the relationship between the severity of reflux esophagitis and esophageal dysmotility and evaluate the effect of prolonged treatment with proton pump inhibitor (lansoprazole 30 mg/day) on esophageal motility in patients with severe reflux esophagitis associated with esophageal motility disorder. Twelve healthy subjects (HS) and 100 patients with reflux disease were involved in the study consisting of two parts: (i) comparison of esophageal motility in HS and patients with non-eroseive reflux disease (NERD), mild esophagitis and severe esophagitis; (ii) effect of 3-6 months lansoprazole therapy on esophageal motility in 23 patients with severe esophagitis, pathologic acid reflux and esophageal peristaltic dysfunction. Results included the following. (i) Esophageal dysmotility was noted in both patients with NERD and erosive GERD. (ii) Severe esophagitis was associated with severe esophageal dysmotility. (iii) Healing of severe esophagitis did not improve esophageal dysmotility. The resting lower esophageal sphincter pressure was 3.9 mmHg (range 1.7-20) before treatment and 4.8 mmHg (range 1.2-18.3) after esophagitis healing (P = 0.23, vs. before treatment), the amplitude of distal esophageal contraction was 28.8 mmHg (range 10.9-80.6) before treatment and 33.3 mmHg (range 10.0-72.5) after esophagitis healing (P = 0.59, vs. before treatment) and the frequency of failed peristalsis was 70% (range 0-100%) before treatment and 70% (range 0-100%) after esophagitis healing (P = 0.78, vs. before treatment). Both esophageal motility disorders and acid reflux play important roles in the mechanism of GERD, especially in severe esophagitis. Esophageal dysmotility is not secondary to acid reflux and esophagitis; it should be a primary motility disorder.     

Esophageal Motility in Low-Grade Reflux Esophagitis, Evaluated by Stationary and 24-Hour Ambulatory Manometry

Whereas previous studies have unequivocally shown that esophageal motility is abnormal in patients with severe reflux esophagitis, the results of motility testing in patients with low-grade esophagitis are inconsistent. We studied 27 patients with Savary grade I and II esophagitis and 24 healthy controls matched for age and sex. Both underwent conventional manometry and 24-h ambulatory pH and pressure monitoring. Esophageal acid exposure was greater in patients than controls. The mean lower esophageal sphincter pressure was significantly lower in esophagitis patients [1.46 ± 0.09 vs. 1.79 ± 0.11 kPa (10.98 ± 0.68 vs. 13.46 ± 0.83 mm Hg)]. The total number of contractions recorded in the 24-h period was not different in the patient group (2168 ± 108.4 vs. 2033 ± 130.5), but esophagitis patients had an increased number of nontransmitted contractions (968 ± 39.4 vs. 773 ± 50.2, p < 0.01). A tendency toward a decreased prevalence of peristaltic contractions just failed to reach statistical significance ( p = 0.07). Both conventional manometry and 24-h monitoring showed no significant difference in peristaltic amplitude between the two groups. Differences in contraction duration (2.02 ± 0.08 vs. 2.39 ± 0.12 s, p < 0.01) and velocity of the peristaltic wave (3.65 ± 0.10 vs. 4.63 ± 0.13 cm/s, p < 0.01) were only detected by 24-h monitoring. The findings made in this study do not support the concept that impaired esophageal peristalsis is a major factor in the pathogenesis of low-grade esophagitis.     

胆碱能神经对反流性食管炎食管动力的影响

目的研究内源性胆碱能神经在反流性食管炎食管动力机制异常中的作用.方法经下食管括约肌切开制备反流性食管炎的猫模型,用连续水灌注测压系统检测正常猫及反流性食管炎的猫食管体部动力;用分光光度法分别测定正常猫及反流性食管炎的猫食管中段、远段肌组织中的乙酰胆碱转移酶和乙酰胆碱酯酶活力.结果反流性食管炎组食管远段平均收缩波幅度明显低于正常对照组(P＜0.0001),食管远段传导速度低于正常对照组(P＜0.05);反流性食管炎时食管中段及远段肌组织中乙酰胆碱转移酶活力均低于正常对照组的中段及远段(P＜0.05及P＜0.0001),以远段更明显(P＜0.0001).反流性食管炎组食管中段及远段肌组织中的乙酰胆碱酯酶活力与对照组比较差异均无显著性(P＞0.05).结论反流性食管炎可导致食管远段动力低下,内源性胆碱能神经功能异常是其重要机制之一.     

Effect of peristaltic dysfunction on esophageal volume clearance

Prolonged esophageal acid clearance, found in some patients with esophagitis, can be attributed in part to the peristaltic dysfunction observed in this population. In this study, we undertook to define the effect of commonly observed peristaltic dysfunction on volume clearance by obtaining concurrent videofluoroscopic and manometric recordings in patients with nonobstructive dysphagia or heartburn. Excellent correlation existed between the findings from the two studies. A single normal peristaltic wave resulted in 100% clearance of a barium bolus from the esophagus. At each recording site, luminal closure, as demonstrated by videofluoroscopy, coincided with the upstroke of the peristaltic pressure complex. Absent or incomplete peristaltic contractions invariably resulted in little or no volume clearance from the involved segment. Regional hypotensive peristalsis was associated with incomplete volume clearance by the mechanism of retrograde escape of barium through the region of hypotensive contraction. The regional peristaltic amplitude required to prevent retrograde escape of barium was greater in the distal compared with the proximal esophagus. The mean peristaltic amplitude associated with instances of retrograde escape was 25 mmHg in the distal esophagus compared with 12 mmHg in the proximal esophageal segments. Thus, the peristaltic dysfunction commonly seen in patients with esophagitis (failed and hypotensive peristalsis) likely leads to impaired volume clearance.     

Manometric study of the lower esophageal sphincter and esophagus in subtotal gastrectomy patients

SUMMARY.  There is controversy in the literature regarding the motor function behavior of the lower esophageal sphincter and esophagus following partial gastrectomy. We studied 26 patients with gastric adenocarcinoma of the distal corpus and/or antrum who underwent radical subtotal gastrectomy with Roux-en-Y reconstruction. There were 15 women (57.69%) and 11 men (42.31%) with a mean age of 57.2 years; 21 were White (80.8%) and five were of African descent (19.2%). Before the surgery and 3 months afterwards, every patient underwent manometric and endoscopic examinations. The lower esophageal sphincter showed reductions in mean respiratory pressure (19.41–15.59 mmHg, P = 0.02) and maximum expiratory pressure (8.13–5.54 mmHg, P = 0.02) without significant alteration in diaphragmatic crura pressure (32.92–30.64 mmHg, P = 0.37). An increase in peristaltic wave amplitude (91.43–124.86 mmHg, P < 0.01) and peristaltic wave conduction velocity (3.29 cm/s to 4.23 cm/s; P = 0.024) were detected in esophageal function. The presence of erosive esophagitis decreased from 10 (38.46%) patients to none ( P = 0.002). We concluded that following surgery the lower esophageal sphincter function was impaired, through decreased pressure in the esophageal component without alteration in diaphragmatic crura pressure. On the other hand, there was significant increase in peristaltic wave amplitude and velocity, and improvement of the erosive esophagitis. The authors suggest that subtotal gastrectomy, with gastroesophageal junction preservation, and Roux-en-Y reconstruction should be the preferred operation for distal gastric cancer to minimize esophageal dysfunction and gastroesophageal reflux disease.     

Dysphagia and esophageal motor dysfunction in gastroesophageal reflux are corrected by fundoplication

Abnormalities in esophageal peristaltic function and acid clearance appear to be responsible for prolonged esophageal acid exposure, a major determinant of the reflux esophagitis and esophageal stricture. We evaluated esophageal motility by manometry in 50 healthy controls and in 35 symptomatic reflux patients before, within 6 months, and 1 year after Nissen fundoplication. Preoperative motility was analyzed in relation to the presence or absence of both nonobstructive dysphagia and erosive esophagitis. We found that (a) preoperative dysphagia was related more to peristaltic dysfunction than to esophagitis; (b) peristaltic wave amplitude and duration were significantly lower than control values in patients with reflux, without correlation to degree of esophagitis or lower esophageal sphincter hypotension; (c) dysphagia ceased in most patients after antireflux surgery at the same time that normal motility was restored independently of lower esophageal sphincter pressure increments. These results suggest that motility disturbances are an important cause of dysphagia in reflux disease, and that reflux is the cause of, rather than the consequence of, peristaltic dysfunction.     

Improvement in Esophageal Motor Dysfunction with Treatment of Reflux Esophagitis: A Report of Two Cases

We report two patients with reflux esophagitis who had decreased lower esophageal sphincter pressures and marked decreased frequency of peristaltic response to swallowing and peristaltic amplitude on pretreatment esophageal motility tracings. Both patients responded to medical therapy of reflux esophagitis with symptomatic clinical improvement, increased lower esophageal sphincter pressures, and increased frequency of peristaltic propagation and amplitude of peristalsis. Measures to treat reflux esophagitis may he effective in some cases, in part, because they permit healing of esophageal inflammation to improve esophageal motor activity, the latter which results in improvement of esophageal acid clearing.     

Secondary oesophageal peristalsis in gastro-oesophageal reflux disease

BACKGROUND AND AIMS: To evaluate the status of secondary oesophageal peristalsis in gastro-oesophageal reflux disease (GORD) and the effect of healing of oesophagitis on these abnormalities. METHODS: Twenty-one patients diagnosed with GORD and 10 control subjects in the same age group were studied. Primary peristalsis was elicited by 10 5 mL water boluses and secondary peristalsis by 10 20 mL boluses of air injected 15 cm above the lower oesophageal sphincter. RESULTS: The pattern of primary peristalsis was normal in a significantly lower number of patients compared with control subjects, six patients (28.6%) versus seven controls (70%), (P<0.05). Similarly, the number of subjects with a normal pattern of secondary peristalsis was also lower in the patient group (zero vs three; P<0.05). A normal primary peristaltic response occurred with 71 (33.8%) of the 210 water boluses in the patients and 73 (73%) of the 100 water boluses in the control subjects, respectively (P<0.001). A normal secondary peristaltic response was seen with 15 (7.1%) of 210 air boluses in patients and 32 (32%) of 100 air boluses in the control subjects (P<0.001). The amplitude of secondary peristaltic waves and the duration of contraction (mean+/-SEM) were significantly lower in patients compared with the control subjects (43.5+/-4.7 vs 89.0+/-13.1 and 3.4+/-0.8 vs 3.9+/-0.3, respectively; P=<0.05). In the 13 patients in whom repeat evaluation was performed after healing of oesophagitis, there was no significant change in the number of patients with normal peristaltic response, number of normal responses to air and water boluses, or amplitude, duration and velocity of peristalsis. CONCLUSION: Significant abnormalities of secondary oesophageal peristalsis occur in patients with GORD and these are not reversed by healing of oesophagitis.     

Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study

The present study analysed whether autologous peripheral blood stem cell transplantation (PSCT) improves engraftment, quality of life and cost-effectiveness when compared with autologous bone marrow transplantation (ABMT). Relapsing progressive lymphoma patients (n = 204; non-Hodgkin's lymphoma n = 166; Hodgkin's disease n = 38) were, after induction treatment with the DHAP-VIM (cisplatin, cytarabine, dexamethasone, etoposide, ifosfamide, methotrexate) regimen, randomly (2:1) assigned to the harvest of granulocyte-macrophage colony-stimulating factor-mobilized stem cells after the second DHAP course or autologous bone marrow cells before the second DHAP course. These stem cells were reinfused following high-dose myeloblative chemotherapy. After induction, 118 patients obtained a partial or complete response and were eligible for randomization. In the PSCT arm (n = 76) significantly faster engraftment of neutrophils [> or = 0.1 and > or = 0.5 x 10(9)/l: 10.7 d (7-36, median, range), 15 (9-45) versus 13 (8-25) and 26 (14-80), P < 0.01] and thrombocytes [> or = 20 x 10(9)/l: 13 d (7-51) versus 18 (11-65), P < 0.01] were observed. In addition, significantly fewer transfusions of red blood cells [6 (0-23) versus 8 (2-24), P < 0.01] and platelets [4 (0-60) versus 8 (2-55), P = 0.01] were required in the PSCT arm. These findings were associated with a significant reduction in the median days of intravenous antibiotics in patients with fever [8.5 (0-30) versus 14 (0-34), P = 0.04] and hospital stay [27 (8-51) versus 34 (24-78), P < 0.05]. Quality of life demonstrated a significant difference in favour of the PSCT arm. Total transplantation costs were significantly lower in the PSCT arm [$13,954 ($4913- 29,532) versus $17 668 ($10,170-44,083) P < 0.05], as a result of the reduced hospital stay and lower antibiotic costs. In summary, these results indicate that PSCT is superior to ABMT with regard to engraftment, supportive care, quality of life and cost.     

Differences in oesophageal bolus transit between patients with and without erosive reflux disease

BACKGROUND: We determined any difference in oesophageal function between reflux patients with and without erosive esophagitis by the application of concurrent manometry and impedance. METHODS: Twenty patients with erosive esophagitis, 20 patients with non-erosive reflux disease, and 15 controls were included in this study. All subjects underwent studies with a catheter containing four impedance-measuring segments and five solid-state pressure transducers. Each subject received 10 liquid and 10 viscous boluses to be swallowed. RESULTS: Healthy controls had greater distal oesophageal peristaltic amplitude than both patient groups (p < 0.05). Normal oesophageal peristalsis was found more frequently in healthy controls than either of the patient groups (p < 0.05). Patients with erosive esophagitis exhibited a lower percentage of complete bolus transit compared to healthy controls and non-erosive reflux disease patients (both p < 0.05). Patients with erosive esophagitis had a longer total bolus transit time compared to healthy controls and non-erosive reflux disease patients (both p < 0.05). CONCLUSIONS: Erosive esophagitis is characterized by longer oesophageal bolus transit and fewer complete bolus transit than non-erosive reflux disease. The noted differences in oesophageal bolus transit may reflect a continuum of dysfunction secondary to increasing oesophageal mucosal damage.     

p47(phox) is required for afferent arteriolar contractile responses to angiotensin II and perfusion pressure in mice

Myogenic and angiotensin contractions of afferent arterioles generate reactive oxygen species. Resistance vessels express neutrophil oxidase-2 and -4. Angiotensin II activates p47(phox)/neutrophil oxidase-2, whereas it downregulates NOX-4. Therefore, we tested the hypothesis that p47(phox) enhances afferent arteriolar angiotensin contractions. Angiotensin II infusion in p47(phox) +/+ but not -/- mice increased renal cortical NADPH oxidase activity (7±1-12±1 [P<0.01] versus 5±1-7±1 10(3) · RLU · min(-1) · μg protein(-1) [P value not significant]), mean arterial pressure (77±2-91±2 [P<0.005] versus 74±2-77±1 mm Hg [P value not significant]), and renal vascular resistance (7.5±0.4-10.1±0.7 [P<0.01] versus 7.9±0.4-8.3±0.4 mm Hg/mL · min(-1) · gram kidney weight(-1) [P value not significant]). Afferent arterioles from p47(phox) -/- mice had a lesser myogenic response (3.1±0.4 versus 1.4±0.2 dynes · cm(-1) · mm Hg(-1); P<0.02) and a lesser (P<0.05) contraction to 10(-6) M angiotensin II (diameter change +/+: 9.3±0.2-3.4±0.6 μm versus -/-: 9.9±0.6-7.5±0.4 μm). Angiotensin and increased perfusion pressure generated significantly (P<0.05) more reactive oxygen species in p47(phox) +/+ than -/- arterioles. Angiotensin II infusion increased the maximum responsiveness of afferent arterioles from p47(phox) +/+ mice to 10(-6) M angiotensin II yet decreased the response in p47(phox) -/- mice. The angiotensin infusion increased the sensitivity to angiotensin II only in p47(phox) +/+ mice. We conclude that p47(phox) is required to enhance renal NADPH oxidase activity and basal afferent arteriolar myogenic and angiotensin II contractions and to switch afferent arteriolar tachyphylaxis to sensitization to angiotensin during a prolonged angiotensin infusion. These effects likely contribute to hypertension and renal vasoconstriction during infusion of angiotensin II.     

Transient Lower Esophageal Sphincter Relaxations and Esophageal Body Muscular Contractile Response in Reflux Esophagitis

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients.     

Effects of low-power argon plasma coagulation thermoablation of Barrett's epithelium on oesophageal motility

INTRODUCTION: Oesophageal dysmotility contributes to the pathogenesis of Barrett's epithelium (BE) allowing prolonged mucosal contact with injurious refluxate. Argon plasma coagulation (APC) is effective for BE ablation, but it is unknown whether the procedure affects oesophageal motility. AIM: To assess the effect of low power (30 W) APC therapy on oesophageal motility in patients with BE. METHODS: Thirty-three patients with at least 4 cm of BE underwent oesophageal manometry before and after APC ablation. All were on proton pump inhibitors. Oesophageal body peristaltic wave duration and amplitude, and lower oesophageal sphincter (LOS) pressure and length were compared before and after treatment. RESULTS: In a total of 28 men and five women, with a mean age of 63.4 years (range 39-79) and mean BE length 6.5 cm (range 4-19), macroscopic clearance was achieved in 28 patients. A small statistically significant (P<0.05) increase in peristaltic wave amplitude was seen after APC [mean (SD) mmHg before versus after: 30.4 (15.2) versus 36.2 (20.1) at 13.5 cm, 47.6 (27.1) versus 54.5 (26.8) at 8.5 cm, and 51.2 (35.3) versus 58 (34.4) at 3.5 cm above the LOS]. No changes in either peristaltic wave duration or LOS parameters [mean (SD) pressure 10.6 (5.6) versus 10.3 (4.3) mmHg; length 2.8 (1.3) versus 2.8 (1.0) cm] were observed. CONCLUSION: APC ablation of BE at a power setting of 30 W does not impair oesophageal motility.     

Ambulatory esophageal pressure and pH monitoring in patients with high-grade reflux esophagitis

Using conventional manometry and 24-hr ambulatory pressure and pH monitoring, we investigated esophageal motility and the esophageal motor response to reflux in 11 patients with reflux esophagitis Savary-Miller grade III and IV, and an age- and sex-matched group of 11 healthy controls. The patients had a significantly increased esophageal acid exposure. Conventional manometry showed a significantly decreased LES pressure and distal peristaltic amplitude in patients. The 24-hr monitoring yielded a significant decrease in peristaltic contraction duration and peristaltic propagation velocity in the patient group. Distal peristaltic amplitude was not decreased. Analysis of the contractions occurring in the 2-min period after each reflux episode showed a reduced number of contractions during the upright period, caused by a significantly decreased number of peristaltic contractions. During the supine period, there was a trend towards an increased number of contractions. It is concluded that esophageal motor activity and the response to reflux are impaired in patients with high-grade reflux esophagitis. However, the abnormalities found are only minor and are unlikely to play an important role in the pathogenesis of reflux esophagitis.     

Lower esophageal sphincter pressure and distal esophageal body function between Hispanic Americans and non-Hispanic whites are equivalent

OBJECTIVE: Esophageal manometry (EM) is the gold standard examination for diagnosis of esophageal motor disorders. Normal values for EM among ethnic groups are not presently available in the literature. The aim of this study was to obtain normal values of EM in adult Hispanic American (HA) volunteers and compare these with those obtained in non-Hispanic white (nHw) volunteers. METHODS: Healthy HA and nHw were recruited from the Albuquerque metropolitan area. Ethnicity was self-reported. Exclusion criteria were symptoms suggestive of esophageal disease, medication use, or concurrent illness that could affect EM. All underwent EM using a solid-state system with wet swallows. Resting lower esophageal sphincter pressure, percent peristaltic contractions, esophageal body contraction velocity, distal esophageal body contraction amplitude, and distal esophageal body contraction duration were measured at end expiration. RESULTS: Forty HA and 24 nHw were enrolled. All subjects completed EM without difficulty. Esophageal body contraction velocity was significantly lower in HA (3.5 cm/s+0.1) than nHw (4+0.1, P=0.01). There were no differences in resting lower esophageal sphincter pressure, percent peristaltic contractions, distal esophageal body contraction amplitude, and distal esophageal body contraction duration. CONCLUSIONS: Esophageal body contraction velocity is slower in normal HA compared with nHw; other EM measures are equivalent between groups. Presently accepted normal values of EM obtained from nHw may be used for HA.     

Nizatidine versus Placebo in Gastroesophageal Reflux Disease: A 12-Week, Multicenter, Randomized, Double-Blind Study

Two doses of nizatidine (150 mg bid and 300 mg hs), an H2-receptor antagonist, were compared with placebo in a 12-wk, multicenter, randomized, double-blind, parallel study in 466 patients with endoscopically documented gastroesophageal reflux disease. Antacid tablets were given concomitantly as needed for pain. Compared with placebo, nizatidine 150 mg twice daily was highly effective in rapidly reducing the severity of heartburn, regardless of esophagitis severity at entry. Significantly greater complete mucosal healing of esophagitis occurred after 6 wk of therapy with nizatidine 150 mg bid (vs. nizatidine 300 mg hs or placebo) only in patients with erosive esophagitis [16/68 (24%) vs. 8/65 (12%)] and erosive and ulcerative esophagitis combined [21/99 (21%) vs. 10/94 (11%)]. At wk 12, healing with nizatidine 150 mg bid was also significantly greater than placebo in erosive [19/68 (28%) vs. 9/65 (14%)], ulcerative [10/31 (32%) vs. 3/29 (10%)], and erosive and ulcerative esophagitis combined [29/99 (29%) vs. 12/94 (13%)]. These results show that twice-daily therapy with nizatidine 150 mg is very effective at relieving heartburn, and can also heal erosive and ulcerative esophagitis. Nizatidine 300 mg hs was not effective in healing esophagitis, compared with placebo.     

牛磺酸通过调控细胞周期蛋白抑制肝星状细胞增殖

目的进一步研究牛磺酸对肝星状细胞(HSC)增殖抑制作用的机制。方法用四甲基偶氮唑盐法检测细胞增殖;流式细胞仪测定细胞周期;免疫细胞化学和实时荧光定量PCR测定细胞周期调控蛋白Cyclin D1和P21waf1表达。结果牛磺酸对HSC增殖具有抑制作用,在浓度为5、10、20,30、40、50 mmol/L 作用48h时的抑制率分别为6.7%、14.4%、23.3%、32.2%、36.7%和45.6%,t值为2.939～6.369,P<0.05～0.01。流式细胞仪检测发现牛磺酸可阻滞HSC由G0/G1期向S期转换,使G0/G1期细胞增多,S期细胞减少。G0/G1期、S期细胞,牛磺酸浓度为40 mmol/L时,分别为(68.2±1.4)%和(26.2±1.3)%,与对照组分别为(56.2±1.7)%和(38.5±0.8)%,差异有统计学意义,t≥5.422,P<0.01。牛磺酸可抑制Cyclin D1表达、促进P21waf1表达,用免疫细胞化学染色结合数码图像分析系统软件分析发现牛磺酸浓度在40 mmol/L时HSC的Cyclin D1表达的平均吸光度为0.13±0.02,P21waf1为0.19±0.02,对照组分别为0.18±0.02和0.14±0.01,差异有统计学意义,t=6.689和t=6.528,P<0.01。实时荧光定量PCR检测也发现经40 mmol/L牛磺酸处理的HSC的Cyclin D1 mRNA表达量(拷贝数与106磷酸甘油醛脱氢酶比值)降低为5776.7±3345.0,对照组为18 400.6±1374.8,而P21waf1 mRNA表达量(拷贝/106磷酸甘油醛脱氢酶)增多为44 866.7±3910.7,对照组为16 933.3±960.9。结论牛磺酸通过抑制Cyclin D1表达、促进P21waf1表达,使HSC阻滞于G0/G1期,而抑制HSC增殖。     

Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with ulcerative colitis

BACKGROUND AND AIMS: Inflammation and thrombosis are closely related processes, which may play a role in the pathogenesis, as well as complications, of inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte aggregation are increased and platelet aggregation is known to occur in the mesenteric vasculature in IBD. The aims of this study were to test the hypotheses that platelet-leucocyte aggregation, platelet activation and neutrophil activation occur in the mesenteric vessels of patients with ulcerative colitis (UC). PATIENTS AND METHODS: Platelet-leucocyte aggregates (PLAs), platelet activation (P-selectin expression) and neutrophil activation (L-selectin expression, which decreases on neutrophil activation) were assessed flow cytometrically in mesenteric arterial, and venous blood sampled in eight patients with UC and eight controls with colonic carcinoma undergoing intestinal resections. RESULTS: In the patients with UC, the number of PLAs in the mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02). In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase was 45%. Mesenteric PLA formation did not occur in patients with colonic carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x 10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5% for controls. No arteriovenous gradient was observed in P-selectin expression, but L-selectin expression (arbitrary units), increased in the mesenteric vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035); P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous 850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for controls. CONCLUSION: The finding of increased numbers of PLAs in the venous mesenteric circulation supports the hypothesis that activated vascular endothelium stimulates PLA formation in UC.