Clinical effects of STW 5 (Iberogast®) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis

Abstract  STW 5, a herbal extract, is effective for the treatment of symptoms in patients with functional dyspepsia (FD). However, its mode of action is still unclear and a modulation of gastric motility is hypothesized. This multicentre, placebo-controlled double-blind study addressed the question of whether STW 5 accelerates gastric emptying in patients with FD and gastroparesis. One-hundred and three patients diagnosed with FD were randomly assigned to a treatment with either STW 5 or a liquid placebo for 28 days. The primary end point of the study was a change of a validated gastrointestinal symptom (GIS) score under treatment. Additionally, patients underwent a ¹³C octanoic acid breath test for the assessment of the gastric half-emptying time ( t _1/2). Patients with prolonged t _1/2 were diagnosed with gastroparesis and requested to repeat the test at the end of treatment. A change of t _1/2 was defined a secondary study end point. t _1/2 was prolonged in 48.6% of patients in the STW 5 group and in 43.8% of the placebo group. During treatment, t _1/2 increased non-significantly in patients treated with STW 5 (+23 ± 109 min; P  = 0.51) and slightly accelerated among patients in the placebo arm (−26 ± 51 min; P  = 0.77) ( P  = 0.49). The improvement of the GIS ( P  = 0.08) and the proportion of patients with a treatment response ( P  = 0.03) were more pronounced in the STW 5 group. Our findings suggest that the clinical effects of STW 5 in patients with FD and gastroparesis are not directly mediated by an acceleration of gastric emptying. A clear-cut correlation with symptom improvement is still lacking.     

The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor

Objective

To investigate the effect of octanoic acid (OA) on the peripheral component of tremor, as well as OA’s differential effects on the central and peripheral tremor component in essential tremor (ET) patients.

COMT-inhibition increases serum levels of dihydroxyphenylacetic acid (DOPAC) in patients with advanced Parkinson's disease

Summary. Inhibition of the catechol-O-methyltransferase (COMT) is an effective treatment for end-of-dose fluctuations in advanced Parkinson's disease. The aim of the present investigation was to analyse the consequences of subsequent alterations in levodopa metabolism under common treat-ment conditions when the levodopa dose is adjusted due to the occurrence of dyskinesias after initiation of the COMT-inhibitor. Ten patients with advanced Parkinson's disease (Hoehn & Yahr stage IV) were medicated with tolcapone. Prior to and five to ten days after the initiation of tolca-pone 300 mg/d, serum level profiles of levodopa and its metabolites (3-O-methyldopa (3-OMD), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)) were performed. The mean daily levodopa dose was reduced from 894 ± 248 mg to 646 ± 252 mg (p = 0.003). There was a significant increase in the area under the curve (AUC) of DOPAC during COMT-inhibition compared to the baseline profile (p = 0.009). There were significant decreases of the AUC of HAV (p = 0.001) and the ratios of the AUC HVA / AUC DOPAC (p = 0.0001) and AUC 3-OMD / AUC levodopa (p = 0.0001). Conclusion: The elevation of DOPAC and the decrease of HVA and HVA / DOPAC reflect a shift of the levodopa metabolism towards the MAO-B dependent oxidative pathway. This might contribute to production of hydroxyl radicals and induction of oxidative stress. Received July 9, 2001; accepted September 28, 2001     

肝性脑病对肝硬化预后的意义

目的 评价肝性脑病对肝硬化患者预后的意义。方法 从肝性脑病等方面评价了150例住院的肝硬化患者，其中47例在住院期间死亡，列为死亡组；103例病情改善，列为存活组。结果 死亡组肝性脑病期别较存活组有显著意义的增高。血清总胆红素水平在治疗过程中有升高趋势，而白蛋白水平则有降低趋势。结论 肝性脑病期别、血清总胆红素、白蛋白水平及变化趋势可较好地反映肝硬化预后。     

杜密克治疗肝硬化引起的肝性脑病的疗效观察

目的 观察杜密克治疗肝硬化引起的肝性脑病的临床疗效.方法 将56例由乙肝或丙肝致肝硬化而出现肝性脑病患者随机分为治疗组(n=32)和对照组(n=24).治疗组接受杜密克口服液,对照组接受常规护肝治疗,经治疗2周后,观察临床疗效、肝功能、血氨、脑电图等变化.结果 杜密克组显效9例(28.1%),有效14例(43.8%),无效9例(28.1%),死亡2例(6.3%),总有效率为71.9%;而对照组显效2例(8.3%),有效3例(12.5%),无效19例(79.2%),死亡5例(20.8%),总有效率为20.8%.两组总有效率比较差异有显著性(P＜0.001).杜密克组血氨浓度显著降低(P＜0.01).结论 杜密克是预防和治疗肝炎肝硬化患者肝性脑病的有效药物,可改善临床症状.     

Helicobacter pylori infection and motor fluctuations in patients with Parkinson's disease

To investigate whether Helicobacter pylori (HP) infection affects the clinical response to levodopa and whether its eradication could improve motor fluctuation in patients with Parkinson's disease (PD). Using the [¹³C] urea breath test, we monitored HP infection in 65 patients with PD and motor fluctuations of the “wearing‐off” or delayed “on” types, with or without dyskinesia. We compared the clinical features and response to L ‐dopa between HP noninfected (n = 30) and HP infected patients (n = 35) by reviewing home diaries kept for 72 hours. Among HP infected patients, we compared the differences in L ‐dopa “onset” time, “on‐time” duration, and scores on the motor examination section of the Unified PD Rating Scale (UPDRS‐III) during the medication “on” phase before and after HP eradication. There were no differences in the age, disease duration, Hoehn and Yahr stage, UPDRS‐III score, L ‐dopa daily dose, and frequency of dyskinesia between HP noninfected and HP infected groups. However, L ‐dopa “onset” time was longer and “on‐time” duration was shorter in HP infected patients than in HP noninfected patients (78.4 ± 28.2 vs. 56.7 ± 25.1 and 210.0 ± 75.7 vs. 257.7 ± 68.9 min, respectively, P < 0.05). HP eradication improved the delay L ‐dopa “onset” time and short “on‐time” duration (to 58.1 ± 25.6 and to 234.4 ± 66.5 min, respectively, P < 0.05). These data demonstrated that HP infection could interfere with the absorption of L ‐dopa and provoke motor fluctuations. HP eradication can improve the motor fluctuations of HP infected patients with PD. © 2008 Movement Disorder Society     

门冬氨酸和鸟氨酸联合治疗肝性脑病的疗效观察

目的观察联合使用门冬氨酸和鸟氨酸治疗各种肝硬化引起肝性脑病患者的临床疗效,探讨其对生化指标的影响。方法收集2004-08～2007-08乙肝、丙肝和酒精性肝硬化住院患者84例,住院期间均出现不同程度的肝性脑病,分为门冬氨酸和鸟氨酸治疗组与乙酰谷酰胺治疗组(各42例),治疗5～7d观察2组患者的临床表现,记录临床症状、体征的变化,检测治疗前后患者血氨和肝功能,判断临床疗效变化。结果2组患者均经过5～7d治疗后,门冬氨酸和鸟氨酸治疗组患者显效22例(52.4%),有效16例(38.1%),无效4例(9.5%),无死亡病例,总有效率为90.5%;乙酰谷酰胺治疗组患者显效16例(38.1%),有效14例(33.3%),无效8例(19.1%),死亡4例(9.5%),总有效率为71.4%。2组总有效率比较,差异有统计学意义(P<0.05)。另外,发现门冬氨酸和鸟氨酸治疗组患者的血氨水平比乙酰谷酰胺治疗组显著下降(P<0.05),而2组之间的血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰转肽酶、胆红素和凝血酶原时间均无明显变化(P>0.05)。结论降低血氨是治疗肝性脑病的重要步骤,门冬氨酸联合鸟氨酸是控制肝性脑病发生的有效药物。     

门冬氨酸和鸟氨酸联合治疗肝性脑病的疗效观察

目的观察联合使用门冬氨酸和鸟氨酸治疗各种肝硬化引起肝性脑病患者的临床疗效，探讨其对生化指标的影响。方法收集2004-08-2007-08乙肝、丙肝和酒精性肝硬化住院患者84例，住院期间均出现不同程度的肝性脑病，分为门冬氨酸和鸟氨酸治疗组与乙酰谷酰胺治疗组（各42例），治疗5～7d观察2组患者的临床表现，记录临床症状、体征的变化．检测治疗前后患者血氨和肝功能，判断临床疗效变化。结果2组患者均经过5～7d治疗后，门冬氨酸和鸟氨酸治疗组患者显效22例（52．4％）．有效16例（38．1％），无效4例（9．5％），无死亡病例，总有效率为90．5％；乙酰谷酰胺治疗组患者显效16例（38．1％），有效14例（33．3％），无效8例（19．1％），死亡4例（9．5％），总有效率为71．4％。2组总有效率比较，差异有统计学意义（P〈0．05）。另外，发现门冬氨酸和鸟氨酸治疗组患者的血氨水平比乙酰谷酰胺治疗组显著下降（P〈0．05），而2组之间的血清谷丙转氨酶、谷草转氨酶、碱性磷酸酶、谷氨酰转肽酶、胆红素和凝血酶原时间均无明显变化（P〉0．05）。结论降低血氨是治疗肝性脑病的重要步骤，门冬氨酸联合鸟氨酸是控制肝性脑病发生的有效药物。     

Recanalisation success is associated with good clinical outcome despite advanced age and stroke severity in patients treated with the Solitaire stentriever

Intravenous recombinant tissue plasminogen activator is associated with significant recanalisation failure in the setting of large artery occlusion. Endovascular treatment by stentriever achieves improved rates of recanalisation but its impact on clinical outcomes remains unclear. We hypothesise that successful recanalisation, unattentuated by age and stroke severity, is associated with improved clinical outcomes in patients treated with the Solitaire stentriever (ev3 Endovascular, Plymouth, MN, USA). We conducted a retrospective study of 60 consecutive acute ischaemic stroke patients treated with the Solitaire stentriever. The data included demographics, vascular risk factors, ictal onset time, National Institutes of Health Stroke Scale (NIHSS) score at presentation, angiographic findings, post-procedure imaging, and clinical follow-up. Recanalisation success was defined as a thrombolysis in cerebral infarction score (TICI) ⩾ 2b. Good clinical outcome was defined as a modified Rankin Scale score (mRS) ⩽ 2 at 3 months. Of the 60 patients, the mean age was 64.1 (standard deviation 13.4) years and 68.3% were men. Median NIHSS score at presentation was 18 (interquartile range 14–22). Successful recanalisation (TICI ⩾ 2b) was achieved in 44 patients (73.3%). Of these 44 patients, 25 patients (56.8%) achieved mRS ⩽ 2 at 3 months. Multiple logistic regression showed significant association between recanalisation success and improved clinical outcome (p = 0.019). Of all patients, four (6.7%) developed symptomatic intracranial haemorrhage. Overall mortality was 28.3%. In conclusion, the Solitaire stentriever was associated with improved recanalisation rates. We showed that successful recanalisation is associated with good clinical outcomes after adjustments for age, sex and stroke severity.     

Motor dysfunction in patients with liver cirrhosis: impairment of handwriting

Motor dysfunction is an important clinical finding in patients with liver cirrhosis and mild forms of hepatic encephalopathy. The mechanisms and clinical appearance of motor impairment in patients with liver cirrhosis are not completely understood. We studied fine motor control in forty four patients with advanced liver cirrhosis (excluding those with hepatic encephalopathy grade II) and 48 healthy controls using a kinematic analysis of standardized handwriting tests. We analysed parameters of velocity, the ability to coordinate and the level of automatisation of handwriting movements. Furthermore, we studied the association between impairment of handwriting and clinical neuro–psychiatric symptoms. As compared with control subjects, patients showed a statistically significant reduction of movement peak velocity in all handwriting tasks as well as a substantial increase of number of velocity inversions per stroke. Using a z–score based assessment we found impairment of handwriting in fourteen out of forty four patients (31.8 %). The deterioration of handwriting was associated with clinical symptoms of motor dysfunction, such as bradykinesia, adiadochokinesia, dysmetria of upper extremities and gait ataxia. This is the first study that quantitatively investigates impairment of handwriting in patients with liver cirrhosis. Our findings suggest the application of kinematic analysis of handwriting for diagnostics of motor dysfunction in patients with mild forms of hepatic encephalopathy.     

雅博司治疗乙肝肝硬化引起的肝性脑病26例疗效观察

目的 观察雅博司治疗乙肝肝硬化引起的肝性脑病的临床疗效。方法 将48例乙肝肝硬化出现肝性脑病患者随机分为雅博司组（26例）和乙酰谷酰胺组（22例）,治疗1周后观察疗效。结果 雅博司组显效12例（46．2％）,有效13例（50％）,无效1例（3.8％）,无死亡,总有效率为96．2％;而乙酰谷酰胺组显效5例（22．7％）。有效7例（31．8％）,无效6例（27．3％）,死亡4例（18．2％）,总有效率为54．5％。两组总有效率比较差异有显著性（P〈0．01）。雅博司组血氨浓度显著降低（P〈0．05）。结论 雅博司是治疗乙肝肝硬化患者肝性脑病的有效药物,可迅速控制惠者的临床症状,降低死亡率。     

Freezing of gait in patients with advanced Parkinson's disease

Summary. Background. Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. Objective. To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. Methods. Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 ± 13.2 years and mean symptoms duration of 11.8 ± 5.6 years were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. Results. The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4–5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). Conclusion. FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment. Received April 19, 2000; accepted June 6, 2000     

Recombinant activated factor VII in an unselected series of cases with upper gastrointestinal bleeding

INTRODUCTION: The mortality rate associated with UGI bleeding remains high at 7-14%. Pharmacologic and endoscopic interventions are the current standard treatment, but there are few alternative options should these fail. This study aimed to assess the efficacy and safety of recombinant activated factor VII (rFVIIa) in the rescue treatment of severe upper gastrointestinal (UGI) bleeding. METHOD: Eleven patients (age: 8-64 years) were treated with rFVIIa at 15.0-90 microg/kg to control UGI bleeds. All three pediatric/adolescent cases and four of the eight adults had UGI hemorrhage associated with liver disease; the origins of the bleeds for remaining adults were trauma (n=1), peptic duodenal ulcer (n=1), hemorrhagic gastritis with sepsis (n=1) and pancreatitis (n=1). RESULTS: Bleeding stopped in seven patients and was markedly reduced in two patients, while there was no change in two patients. Coagulation parameters displayed a tendency to improve, and transfusion requirements were reduced in most patients. In total, five patients died within 2 weeks of rFVIIa treatment. In each case, fatality was judged unrelated to rFVIIa treatment. No thromboembolic events occurred. CONCLUSIONS: These results suggest that, even if our data are optimistic, the use of rFVIIa in the treatment of severe UGI bleeding warrants further investigation in prospective, randomized trials.     

Serum uric acid levels in patients with Parkinson's disease: Their relationship to treatment and disease duration

There is evidence to support that oxidative stress is increased in Parkinson's disease (PD) and contributes to degeneration of dopaminergic neurons. Uric acid (UA), a natural antioxidant in blood and brain tissue, scavenging superoxide, peroxynitrite and hydroxyl radical, was found reduced in the serum of PD patients. In addition low plasma uric acid (UA) levels have been associated with an increased risk of PD.

Objectives

The aim of our study was to investigate serum UA levels in PD patients compared with age-matched healthy controls and their possible relationship with several clinical parameters of PD and pharmaceutical treatment.

Patients and methods

We measured serum UA levels in 43 PD patients and 47 healthy volunteers, age and sex-matched. UA levels were correlated with disease duration, severity and treatment.

Results

Low UA levels were observed in PD patients compared with controls (p = 0.009). Age, Body Mass Index (BMI) and UPDRS III score did not significantly affect serum UA concentrations, whereas gender was found to contribute significantly to UA level (p < 0.000). Strong and significant inverse correlations of UA with disease duration (R_s = −0.397, p = 0.009) and daily levodopa dosage (R_p = −0.498, p = 0.026) were observed. These associations were significant for men (R_s = −0.441, p = 0.04 and R_s = −0.717, p = 0.03 respectively), but not for women (R_s = −0.221, p = 0.337 and R_s = −0.17, p = 0.966 respectively).

Conclusion

Our results suggest that there may be increased consumption of UA as a scavenger in PD, possibly heightened by dopaminergic drug treatment. Given the antioxidant properties of UA, manipulation of its concentrations should be investigated for potential therapeutic strategies of the disease.     

综合降低血氨浓度治疗乙肝肝硬化引起的肝性脑病

目的通过综合降低血氨浓度,观察治疗乙肝肝硬化引起的肝性脑病的临床疗效。方法将56例乙肝肝硬化出现肝性脑病患者随机分为综合降低血氨治疗组（包括口服乳果糖、醋酸灌肠、乙酰谷酰胺静脉注射,n=30）和乙酰谷酰胺治疗组（n=28）,1周治疗后观察临床疗效。结果综合治疗组显效21例（70．0％）,有效9例（30．0％）,无效0例,无死亡,总有效率100％;而乙酰谷酰胺治疗组显效8例（28．6％）,有效8例（28．6％）,无效7例（25．0％）,死亡5例（17．8％）,总有效率为57．1％,2组总有效率比较差异有统计学意义（P〈0．001）。综合治疗组死亡率和血氨浓度也显著降低（P〈0．05）。结论综合降低血氨浓度是控制乙肝肝硬化患者肝性脑病的有效方法,可显著降低肝性脑病的发生,降低患者死亡。