[Assessment of the efficacy and safety of the phytopharmacon STW 5 versus metoclopramide in functional dyspepsia--a retrolective cohort study]. / Wirksamkeit und Unbedenklichkeit des Phytopharmakons STW 5 versus Metoclopramid bei funktioneller Dyspepsie unter Praxisbedingungen--eine retrolektive Kohortenstudie.

AIM: The objective of this study was to assess the efficacy and safety of the phytopharmacon STW 5 versus metoclopramide in functional dyspepsia. METHODS: A retrolective, epidemiological cohort study with parallel groups in 23 randomised centres where both drugs were used routinely was performed. The main outcome variable was improvement of 10 dyspepsia-specific symptoms of a valid gastrointestinal symptom score (GIS) during therapy. For inclusion, patients had to suffer from at least three of these symptoms before therapy. Secondary outcome variables were change of single symptoms, time till complete symptom relief, investigators' judgement of efficacy and tolerability, duration of inability to work and occurrence of adverse events. RESULTS: The per protocol collective comprised 490 STW 5 and 471 MCP patients. Anamnestic data were comparable. 439 of patients had taken MCP as drops. There was no relevant difference in median treatment duration. Significantly more patients were symptom-free after STW 5 treatment (71.6 vs. 62.8% p = 0,012). Additionally, the extent of symptom improvement (excluding nausea and vomiting) and median duration of inability to work (1 vs. 3 days) were significantly different in favour of STW 5. More physicians assessed STW 5 as effective (71.6 vs. 63.1% p<0.01) and very well tolerated (90 vs. 70.6% p<0.001). Adverse drug reactions were documented only under MCP. CONCLUSION: The present study illustrates a comparable to higher efficacy of STW 5 vs. MCP with better tolerability in treating functional dyspepsia under practice conditions, especially regarding complete symptom improvement, symptom duration and quality of life. The study confirms the results of prospective trials for STW 5 as being an appropriate alternative to the frequently administered antacids and prokinetics.

Phytotherapy for functional dyspepsia: a review of the clinical evidence for the herbal preparation STW 5.

Functional gastrointestinal disorders such as functional (or non-ulcer) dyspepsia are characterized by a broad spectrum of symptoms referred to the upper abdomen without a detectable cause utilizing routine diagnostic measures. It is now believed that disordered gut function (including abnormalities like disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function) play a key role for the manifestation of these disorders. The underlying pathophysiology is not yet fully understood. However, the available data suggest that a number of factors may contribute to the manifestation of symptoms. These factors include environmental factors such as acute infections as trigger event, psychological stressors that may precede acute exacerbations and a genetic predisposition. Considering the large number of mechanisms, a treatment targeting a single mechanism is unlikely to be effective in all patients. Indeed, chemically defined treatments usually gain a 10-15% superiority over placebo. In recent years placebo-controlled studies have demonstrated superiority of a commercial multicomponent herbal preparation, STW 5, with the trade name Iberogast, for the treatment of patients with functional dyspepsia and irritable bowel syndrome. This phytopharmacon is a combination of nine plant extracts each with a number of different active constituents. Pharmacological studies have shown different effects of the single plant extracts on the (molecular) mechanisms which are discussed as underlying the manifestation of symptoms. Various well-controlled clinical trials have independently confirmed clinical efficacy and safety. The clinically efficacy of this multicomponent herbal preparation questions the current trend of highly targeted drug molecules that usually target one single receptor population while it has not been shown that a single receptor group plays a pivotal role for the control of symptoms. Herbal medicines are obtained from various plants and contain complex extracts with a large number of different active substances. While there are only limited head-to-head comparisons with conventional chemically defined medications, the combination of extracts with various gastrointestinal active ingredients appears to be advantageous for a heterogeneous condition such as functional dyspepsia.

[The efficacy of a combination herbal medicine in the treatment of functional dyspepsia. Meta-analysis of randomized double-blind studies on the basis of a valid gastrointestinal symptom profile]. / Wirksamkeit eines pflanzlichen Kombinationspräparats bei funktioneller Dyspepsie. Metaanalyse randomisierter Doppelblindstudien auf Basis eines validen gastrointestinalen Symptomprofils.

BACKGROUND AND AIM: Functional dyspepsia is a heterogeneous clinical entity of incompletely known etiology. Overall, four randomized double-blind studies from the nineteen-nineties investigating acute treatment of this condition with the combination herbal medicine Iberogast, are available. A meta-analysis of the studieswas carried out to evaluate the overall therapeutic effect. PATIENTS AND METHODS: In all four, triple-arm, controlled multicentre studies, the efficacy of 4 weeks of treatment with 3 x 20 drops daily, applied after a washout phase, was investigated, the primary efficacy parameter being a specific gastrointestinal symptom score. Of the 592 participants in the studies, 196 were treated with Iberogast, 131 with placebo, and 61 with cisapride as positive control. The remaining 204 patients, who were treated with an experimental herbal preparation of similar composition, were not admitted to the final analysis. RESULTS: While overall appreciable improvement of the clinically relevant symptoms of moderate severity was seen under treatment with the combination herbal preparation, the individual studies differed in terms of the statistical significance of the results obtained. The meta-analysis of studies revealed a clear therapeutic effect for the herbal medicine (p < 0.0001). CONCLUSION: The clinical experience with the combination preparation for the treatment of functional dyspepsia was confirmed by the meta-analysis of the modern double-blind studies.

Effect of polyunsaturated phosphatidyl-choline on lipid transport system in alcoholic liver injury.

The aim of this study was to determine whether serum lipid composition and lipolytic activities in alcoholinduced liver dystrophy were modified by the co-administration of polyunsaturated phosphatidylcholine (PPC). Chronic alcohol intoxication was induced in rats by intragastric ethanol administration of 3.5 g/kg body weight per day over 56 days. Aqueous PPC suspension was given intragastrally in doses of 100 and 300 mg/kg body weight. Chronic alcohol intoxication led to the development of protein and lipid dystrophy of hepatocytes. PPC partially prevented alcoholic injury of the liver cells and had a normalizing effect on cholesterol esterification, lipolysis of lipoproteins and on the fatty acid composition of the main lipoprotein classes.

Hepatic and pancreatic effects of polyenoylphosphatidylcholine in rats with alloxan-induced diabetes.

Polyenoylphosphatidylcholine (PPC: 100 or 300 mg kg-1 b.w., by gastric intubation for 30 days) produced a clearcut protection of the liver of rats treated with alloxan (150 mg kg-1 b.w., i.p.). The liver of rats treated with alloxan was characterized by hydropic dystrophy and lymphocytic infiltrations. Treatment with alloxan increased serum gamma-GT and ALAT activities. The liver structure of rats treated with PPC did not differ from the liver of control animals. PPC normalized the biochemical abnormalities caused by the diabetes. The number of pancreatic islets and beta/alpha cell ratio decreased in the diabetic rats. A number of beta-cells in this group did not contain granules. PPC prevented the decrease in the number of islets and the beta/alpha cell ratio in the pancreas of the diabetic rats. The intensity of staining of beta-cell granules in the pancreas of PPC-treated rats had a position intermediate between the control and diabetic groups. Alloxan increased the blood glucose content where treatment with PPC decreased this. The results suggest that PPC acts as a cytoprotector in the liver and pancreas of rats with experimental diabetes induced by alloxan.

"Essential" phospholipids versus nicotinic acid in the treatment of patients with type IIb hyperlipoproteinemia and ischemic heart disease.

In patients with moderate, dietary noncorrigible hyperlipoproteinemia type IIb and ischemic heart disease, treatment with nicotinic acid is limited by the side effects of the drug. In 100 patients, 6-month treatment with nicotinic acid (n = 50) or "essential" phospholipids (EPL); Lipostabil, manufacturer: Rhône-Poulenc Rorer) (n = 50) indicated comparable efficacy for both substances: Significant (p < .001) reductions of serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride values were similar in both groups, while nicotinic acid increased high-density lipoprotein (HDL) cholesterol significantly (p < .01) better than Lipostabil. A detailed analysis of ultracentrifugal lipoprotein profiles, hydroperoxide concentrations in LDL, and cholesterol-accepting properties of HDL in a small number of Lipostabil- and nicotinic acid-treated patients revealed favorable shifts in the lipoprotein profile, significant (p < .05) reductions of LDL hydroperoxides, and favorable increases of the most antiatherogenic HDL2b subfraction only in the Lipostabil-treated group. Clinically, both medications reduced the intensity and number of angina pectoris attacks per week (p < .05), but only Lipostabil-treated patients significantly (p < .05) increased their working capacity in the veloergometric test. Since in the nicotinic acid-treated group dropouts (nine patients, eight related to the drug) and side effects [14] exceeded those in the Lipostabil-treated group (two dropouts not related to the drug, no side effects), it is suggested that Lipostabil is a preferable alternative in the treatment of patients with moderate, dietary noncorrigible hyperlipoproteinemia IIb and ischemic heart disease.

[Absorption of di-linoleoylphosphatidylcholine after oral administration]. / Resorption von Dilinoleoyl-phosphatidylcholin nach oraler Gabe.

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e. the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1-linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in linoleic acid, and into the serum triglycerides was observed with peak values of 2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1-linoleoyl-PC into the liver after oral application of drugs containing such species in high amounts like "essential" phospholipids with about 50% of DLPC let expect therapeutic effects on membranes into which this special species is incorporated.

Comparison of a charcoal sorbent fiber with commercial charcoals for hemoperfusion.

A charcoal sorbent fiber (Enka, F.R.G.), was assessed for impurities, surface area, and adsorptive properties of its native charcoal, and compared with other uncoated activated charcoals. In vivo and in vitro hemocompatibility of the fiber were assessed as well as the adsorptive properties for endogenous toxins. The charcoal of the fiber had few impurities and a high surface area of 1,200 m2/g charcoal. For measuring the adsorptive speeds, 2 g of the uncoated charcoals were milled and screened to a particle size of 150-250 microns (Enka; 30-40 microns) and then mixed with the solutions of the individual solutes. The charcoal types of Enka, used in the charcoal sorbent fiber, and of Sutcliffe Speakman, used in the acrylic hydrogel coated charcoal, exhibited the highest adsorptive rates for bromthalein (middle molecular weight marker) and inulin (high molecular weight marker). No hematological differences among the various charcoals were found during the in vivo hemoperfusions. In the in vitro hemoperfusions with heparinized fresh blood, the fibers showed the lowest loss of leucocytes and thrombocytes. In the in vitro evaluation of the absorbents for hepatic support, the charcoal fiber and the petroleum pitch charcoal of Asahi had the best adsorptive properties for substances in the low molecular weight range.

[Serum concentrations of alpha 1-fetoprotein in acute hepatic failure treated by hemoperfusion with baboon livers (author's transl)]. / Serumkonzentration von Alpha 1-Fetoprotein bei extrakorporaler Pavianleberperfusion zur Behandlung von Patienten mit akutem Leberversagen.

9 patients with acute hepatic necrosis following virus hepatitis or hepatic intoxication and 2 patients with acute necrosis of cirrhotic liver, all with stage IV or V hepatic coma, were treated by hemoperfusions with baboon livers. Serum levels of alpha 1-fetoprotein (AFP) were examined prae-, intra- and post perfusion by radioimmunoassay. In 4 patients who survived, the AFP-levels increased from 20 to 65 ng/ml to 180 to 480 ng/ml and remained raised for more than one week. In the patients who died of liver insufficiency, the AFP-levels were only slightly or temporarily increased. The alpha 1-fetoprotein determination is a reliable criterium for the prognosis of hepatic coma patients treated by hemoperfusion.

Treatment of acute hepatic failure by hemoperfusion over baboon and human livers: alphafetoprotein levels in serum.

Twelve patients with acute liver failure, two patients with cirrhotic failure of the liver, and one patient in the terminal stage of cirrhotic liver were treated. The patients had grade IV or V hepatic coma. Twenty-seven perfusions were carried out, each lasting 8 to 27 hours, with one to four perfusions per patient. Eight patients with acute liver failure were brought out of the coma. Six of them showed sufficient clinical symptoms of hepatic regeneration; five of these could be discharged. These results suggest that 50% of complete clinical recovery of consciousness from grade IV or V coma in acute hepatic failure is possible with this therapy. The three patients with liver cirrhosis treated with a total of five hemoperfusions did awaken, but died because of insufficient hepatic regeneration. The serum alphafetoprotein (AFP) levels were examined. In those patients brought out of the coma, a rapid increase of AFP up to 260--500 ng/ml was observed. These levels remained high for several weeks in the patients who survived. In the patients who died of liver insufficiency, AFP levels increased only slightly or briefly, so AFP could be a good criterion for determining the prognosis for coma patients with this treatment.

[A humoral transfer factor preventing rejection of allotransplanted rat liver? (author's transl)]. / Ist der humorale Transferfaktor für die Reaktionslosigkeit von Rattenleberallotransplantaten verantwortlich?

We grafted orthotopically 11 DA and 20 WiS-livers into LEW. The recipients of DA-livers survived 10.5 +/- 4.3 days; of the 20 recipients of WiS-liver, however, nine survived 18-37 days, and the other 11 survived indefinitely. The cells of recipients who survived more than 4 months showed GvHR of grade III, and their transfer showed no significant immunosuppressive effect. The indefinitely surviving liver recipients could accept specific skin grafts, but normally rejected third party skin. The serum of these recipients was able to prolong the survival of kidney grafts. This transfer factor is in our estimation responsible for the prolonged survival of rats with liver grafts.

Problems of competition in charcoal hemoperfusion for the treatment of intoxications.

Both toxic and physiological substances are adsorbed during an extracorporeal hemoperfusion for the treatment of exogenous and endogenous intoxications. Using a closed circuit in vitro, we perfused one liter saline or fresh human plasma with 4425 mumol creatinine, 4854 mumol and 97,086 mumol barbital-Na, 597 mumol bromthalein, 1942 mumol and 29,126 mumol raffinose, and 200 mumol inulin in different combinations over 70 gm of uncoated charcoal with the following results: 1. The adsorptive capacity of other substances is not influenced by preadsorption of the charcoal with a low or middle molecular weight substance; 2. In the low and middle molecular weight range, there is no competition between two substances in a solution; 3. The simultaneous usage of two substances of middle and high molecular weight, or preadsorption with a high molecular weight substance, reduces the rate of adsorption and the capacity of charcoal for middle molecular weight substances, but not for low molecular weight substances.

Suppression of cell-mediated immunity in rats transplanted with kidneys from donors compatible at the major histocompatibility complex.

In order to study the immunological status of rats transplanted with H-1-compatible kidney allografts, LEW rats were grafted with F and (Fischer X Lewis)F1 (FLEWF1) kidneys. Most of the F kidneys were rejected within 55 days, only 4 of 24 surviving for more than 4 months. However, two-thirds of the FLEWF1 recipients survived for more than 4 months, the others having died within 64 days. During the first postoperative week, high levels of serum lymphocytotoxic antibodies were found in recipients of F kidneys, and thereafter there was little change. In this respect these rats did not differ from recipients of kidneys with major histocompatibility differences. However, recipients of FLEWF1 kidneys had low haemagglutinating and lymphocytotoxic antibody titres. No serum-blocking factor could be found in kidney of recipients by use of the microcytotoxicity assay (MCA) or inhibition of allorosette formation. Cellular immunity, which was studied by means of the graft-versus-host reaction (GVHR) and the microcytotoxicity assay, was detected in the first postoperative week. This immunity gradually declined, and after 6 weeks it was no longer detectable. The immunological status of the long-term surviving kidney recipients remained unchanged, even when they were provided with further antigenic challenge in the form of two successive donor strain skin grafts.

[Possibilities to avoid adsorption of physiological substances during charcoal hemoperfusion (author's transl)]. / Möglichkeiten zur Vermeidung der Adsorption physiologischer Substanzen bei der Aktivkohlehämoperfusion.

For the clinical use of charcoal in intoxications the loss of normal substances out of the organism must be avoided. In order to study the possibility of pretreating the charcoal with certain substances without influencing the adsorptive capacity of toxic metabolic products we perfused over 70 g uncoated charcoal for 6 h: 500 mg creatinine, 1 g and 20 g barbital, 500 mg bromthalein, 1 g raffinose resp. 1 g inulin per litre physiological saline in different combinations and found the following results: 1. In low and middle molecular weight levels there is no competition between two substances. 2. By preadsorption of the charcoal with a low or middle molecular weight substance, the adsorptive capacity of other substances is not influenced.

[Extracorporeal perfusion with baboon liver in the treatment of hepatic coma (author's transl)]. / Die extrakorporale Perfusion mit Pavianlebern zur Behandlung des Leberzerfallskomas.

In 11 patients with hepatic coma (stage IV and V according to Abouna) extracorporeal haemoperfusion using the Scribner shunt (radial or profunda femoris artery) was performed over 12 to 27 hours with 22 baboon and one human livers. Eight patients emerged from coma, six of them showed sufficient regeneration of the diseased liver. Four patients were discharged as cured, one patient died of acute pancreatic necrosis, a further one due to bleeding from an old gastric ulcer. In the 2 remaining patients the coma recurred within 48 hours. Tree patients never came round from coma. After perfusion no antibodies against baboon proteins were demonstrable in the patients. Thus there is very little danger of an anaphylactic reaction when perfusion is repeated. The titre of preformed cytotoxic antibodies against baboon cells in patients' serum rises only after 1-2 weeks and decreases again after 4 weeks. In our experience extracorporeal liver perfusion with baboon or human livers is the most promising method for treatment of hepatic coma.