[Update chronic viral hepatitis]. / Update chronische Virushepatitis.

More than 500,000 people in Germany have chronic viral hepatitis. The interferon-based treatments formerly used in hepatitis B have been widely replaced by life-long oral medication with nucleoside or nucleotide analogues. Treatment for chronic hepatitis C has been improved substantially by the development of new and very expensive drug combinations. Up to 90% of patients can now be cured with certainty, and one to two years after successful treatment there is no relevant risk of recurrence. These individuals expect to receive insurance cover under appropriate conditions. Vaccination programmes are very efficient at decreasing the incidence of hepatitis B, but no vaccine against hepatitis C is likely to become available in the next decade.

[Biologics--the new horizon for medical therapy]. / Biologika--der aktuelle Mega-Trend in der Arzneimitteltherapie.

Biologics include a wide range of medications that are produced by means of biological processes involving recombinant DNA technology. Approximately one in four of the recently approved new therapeuticals belongs to this group. Biologics have added major therapeutic options for the treatment of many diseases with an especially profound impact on rheumatoid arthritis, chronic inflammatory bowel disease, psoriasis, multiple sclerosis and a great array of malignancies. Many more targets are already screened in clinical research. Despite their clinical promises, monoclonal antibodies are raising concern about the potential adverse effects of long-term use. Costs are dramatically higher than for conventional medications, raising severe pharmacoeconomic concerns.

[Bile acid-independent effect of hymecromone on bile secretion and common bile duct motility]. / Gallensäure-unabhängige Wirkung von Hymecromon auf die Gallesekretion und die Motilität der Gallenwege.

BACKGROUND AND OBJECTIVE: Hymecromone (4-methyl-umbiliferone) has been used for more than 20 years for the treatment of functional and obstructive spasms of the biliary tract. Its mode of action however is still largely unknown. We investigated the effect of 4-methyl-umbiliferone p. o. and i. v. on gall bladder and common bile duct motility and studied potentially indirect effects via alterations in bile acid metabolism. PATIENTS AND METHODS: Twenty healthy volunteers, aged 25 - 37, 10 males, 10 females, were included into a Placebo-controlled, randomised, cross-over double-blind study. Subjects were treated with 800 mg hymecromone p. o.; in addition a standardized meal (Biloptin, 40 gs) was given. Gall bladder volume and common bile duct diameter were determined by ultrasound. Conjugated and unconjugated bile acids were analysed by gas chromatography. Additionally, in a third open label phase hymecromone was given i. v. RESULTS: Common bile duct diameter was significantly larger after a standard meal with hymecromone given p. o. or i. v. than with placebo (each p < 0.01). However, alterations in gall bladder volume after a standard meal were not different between placebo and hymecromone (p. o. or i. v.). Unconjugated and conjugated bile acids rose after standard meal in all three groups without significant differences between hymecromone and placebo. CONCLUSIONS: Hymecromone was associated with significant dilation of the common bile duct. In contrast to previous reports an effect of hymecromone on gall bladder motility could not be observed. The unchanged values of bile acids in serum after hymecromone compared to placebo, together with the dilatation of the common bile duct after hymecromone, may indicate a bile acid-independent effect of hymecromone on bile secretion.

[Development and current status of non-specific enzyme therapy]. / Entwicklung und aktueller Stellenwert der unspezifischen Enzymtherapie.

Non-specific enzyme therapy does not intend the catalysis of definite steps of metabolism, but claims to stimulate regenerative processes in general. Initially, non-specific enzyme therapy had been considered to be a promising approach. The growing knowledge in basic research and the lack of evidence for clinical effectiveness rendered the predominantly oral application of enzyme preparations for non-specific treatment outdated by the 1960s. In Germany, however, the absence of strict legal regulations prevented the deregistration of drugs designed for non-specific enzyme therapy. Furthermore, numerous clinical studies were initiated by the leading producer of enzyme preparations in Germany in order to provide the scientific confirmation missing so far. Our critical and systemic review of the published trials shows that neither the mechanism of action could be enlightened, nor the clinical benefit of non-specific enzyme therapy proven on an acceptable level of scientific standards.

[Autologous chondrocyte transplantation--progress or misleading development in high-tech medicine?]. / Autologe Chondrozytentransplantation--Fortschritt oder Irrweg der Hightech-Medizin?

Autologous chondrocyte transplantation (ACT) is a recently developed procedure for repairing chondral defects of the knee. An analysis of the literature provides no evidence so far for regular regeneration of hyaline cartilage, and no randomized controlled studies are available showing a long-term efficacy. Therefore, controlled randomized studies are urgently needed. At present, ACT cannot be recommended for extended application in clinical practice.

[Health management in private health insurance]. / Gesundheitsmanagement in der Privaten Krankenversicherung.

German private health insurance faces new challenges. The classical tools of cost containment are no longer sufficient to keep up with ever increasing expenses for health care, and international competitors with managed care experience from their home markets are on the point of entering business in Germany. Although the American example of managed care is not fully compatible with customer demands and state regulations, some elements of this approach will gradually be introduced. First agreements were signed with networks or individual preferred providers in outpatient care and rehabilitation medicine. Insurance companies become more and more interested in supporting evidence based guidelines and programmes for disease and case management. The pros and cons of various other health management tools are discussed against the specific background of the quite unique German health care system.

A simple and rapid method to gain high amounts of manganese peroxidase with immobilized mycelium of the agaric white-rot fungus Clitocybula dusenii.

The agaric basidiomycete Clitocybula dusenii was used for the production of the extracellular ligninolytic enzyme, manganese (Mn) peroxidase. An immobilization technique is described using cellulose and polypropylene as carrier for the fungal mycelium. High amounts of Mn peroxidase were obtained with agitated cultures of immobilized fungus (up to 3,000 U l(-1)) while the biomass was recovered and used for further production cycles. Purification of Mn peroxidase revealed the existence of two forms: MnP1 (molecular mass 43 kDa, pI 4.5) and MnP2 (42 kDa, pI 3.8).

[Subarachnoid hemorrhage as life-threatening complication of neural therapy. Case report]. / Subarachnoidalblutung als lebensbedrohliche Komplikation nach Neuraltherapie. Fallbericht.

In Germany, neural therapy is a frequently used method of complementary medicine. It is based on the hypothesis, that pathologically altered regions may cause symptoms in other, distant localizations and that this process can be interrupted by the local injection of anesthetic drugs. Since the pathogenetic acting regions are supposed to occur in any part of the body, neural therapy is not limited to superficial injections, but also includes injections into deep structures and internal organs. Supporters of this therapeutic approach always claim that these procedures are free of risk if carried out by an experienced therapist. We report the case of a young woman, who suffered subarachnoidal bleeding caused by an attempt to infiltrate the tonsilla pharyngea during a neural therapeutic treatment. The analysis of this incident shows that severe and even life threatening complications cannot be ruled out in all neural therapeutic injections, even if they are performed strictly according to the rules given in the textbooks of neural therapy.

Degradation of lignite (low-rank coal) by ligninolytic basidiomycetes and their manganese peroxidase system

Ligninolytic basidiomycetes (wood and leaf-litter-decaying fungi) have the ability to degrade low-rank coal (lignite). Extracellular manganese peroxidase is the crucial enzyme in the depolymerization process of both coal-derived humic substances and native coal. The depolymerization of coal by Mn peroxidase is catalysed via chelated Mn(III) acting as a diffusible mediator with a high redox potential and can be enhanced in the presence of additional mediating agents (e.g. glutathione). The depolymerization process results in the formation of a complex mixture of lower-molecular-mass fulvic-acid-like compounds. Experiments using a synthetic 14C-labeled humic acid demonstrated that the Mn peroxidase-catalyzed depolymerization of humic substances was accompanied by a substantial release of carbon dioxide (17%-50% of the initially added radio-activity was released as 14CO2). Mn peroxidase was found to be a highly stable enzyme that remained active for several weeks under reaction conditions in a liquid reaction mixture and even persisted in sterile and native soil from an opencast mining area for some days.

Biodegradation of lignin by white rot fungi.

A review is presented related to the biochemistry of lignocellulose transformation. The biodegradation of wood constituents is currently understood as a multienzymatic process with the mediation of small molecules; therefore, this review will focus on the roles of these small molecular compounds and radicals working in concert with enzymes. Wood rotting basidiomycetous fungi penetrate wood and lead to more easily metabolized, carbohydrate constituents of the complex. Having a versatile machinery of enzymes, the white rot fungi are able to attack directly the "lignin barrier." They also use a multienzyme system including so-called "feed back" type enzymes, allowing for simultaneous transformation of both lignin and cellulose. These enzymes may function separately or cooperatively.

Degradation of Soil Humic Extract by Wood- and Soil-Associated Fungi, Bacteria, and Commercial Enzymes.

> Abstract An alkaline humic extract (HE) of a black calcareous forest mull was exposed to 36 fungal and 9 eubacterial isolates in liquid standing culture. At 21 d in fungi, and 4 d in bacteria, the groups of wood-degrading basidiomycetes, terricolous basidiomycetes, ectomycorrhizal fungi, soil-borne microfungi, and eubacteria had reduced the absorbance (A340) of HE media by 57, 28, 19, 26 and 5%, respectively. Gel permeation chromatography revealed that the large humic acid molecules were more readily degraded than the smaller fulvic acid molecules and served as a sole source of carbon and energy. The more active HE degraders reduced the overall molecular weight of humic and fulvic acids by 0.25 to 0.47 kDa. They also reduced the chemical reactivity of HE to tetrazotized o-dianisidine, indicating the degradation of hydroxylated aromatic molecules (which are responsible for this reaction). Decreases in absorbance, molecular weight, and reactivity were caused by fungal manganese peroxidase, horseradish peroxidase, beta-glucosidase, and abiotic oxidants such as H2O2 and Mn(III) acetate. It is concluded that fungi, some of which are propagated in contaminated soils to control xenobiotics, metabolize HE compounds enzymatically. They use enzymes which are also involved in the degradation of soil xenobiotics. Because of reductions in the molecular weight of HE, which is a potential carrier of heavy metal ions and xenobiotics, solubility and motility of humic substances in soil and surface waters are increased.

Degradation of humic acids by manganese peroxidase from the white-rot fungus Clitocybula dusenii.

The depolymerization of humic acids (HAs) obtained from low-rank coal (lignite) to fulvic acids (FAs) was investigated in a cell-free system (in vitro) using manganese peroxidase (MnP) from the white-rot fungus Clitocybula dusenii b11. MnP was produced in surface cultures of C. dusenii which were induced with manganese (II) ions (Mn2+, 300 microM). The optimum conditions for the action of MnP were determined by varying following parameters of the enzyme assay: i) concentration of Mn2+, ii) concentration of hydrogen peroxide (H2O2), iii) pH value and iv) temperature. Optimum parameters determined were used in subsequent in vitro depolymerization studies of humic acids. For that purpose, following parameters of the reaction mixture were additionally varied: concentration of HAs, concentration of the thiol mediator glutathione (GSH), presence and concentration of organic solvents. As the result, following parameters were found to be optimal for the MnP-catalyzed in vitro depolymerization of HAs into low-molecular weight FAs (MnP activity 0.12 U/ml): 250 micrograms/ml HAs, 1 mM MnCl2, 46 microM/min H2O2 (continuously supplied by glucose oxidase), 600 microM GSH, 4% (v/v) N,N-dimethylformamide (DMF), pH 4.0, and 37 degrees C.

Oxidative decomposition of malonic acid as basis for the action of manganese peroxidase in the absence of hydrogen peroxide.

Manganese peroxidase (MnP) from the ligninolytic basidiomycetes Phlebia radiata and Nematoloma frowardii was found to decompose malonate oxidatively in the absence of H2O2 in a reaction system consisting of the enzyme, sodium malonate and MnCl2. The enzymatic oxidation resulted in a substantial decrease in malonate concentration and the formation of CO2, oxalate, glyoxylate and formate. Simultaneously with the decomposition of malonate, Mn(II) was oxidized to Mn(III) leading to high transient concentrations of the latter. MnP action in the absence of H2O2 started slowly after a lag period of 3 h. The lag period was considerably shortened after a single addition of Mn(III). Superoxide dismutase and catalase inhibited the enzymatic reaction partly, ascorbate completely. ESR studies demonstrated the formation of a carbon-centered radical during the course of the reaction. We propose that the latter generates peroxides that can be used by MnP to oxidize Mn(II) to Mn(III).

Assessing HCFA's Health Care Quality Improvement Program.

BACKGROUND: In 1992 the Health Care Financing Administration introduced the Health Care Quality Improvement Program (HCQIP), through which quality improvement projects are conducted in partnership with quality improvement organizations (QIOs), hospitals, health plans, or physicians. An evaluation of HCQIP began in May 1996 in response to the QIOs' request for an independent assessment of their activities. METHODOLOGY: The methodology and objectives of the evaluation were determined by an independent panel. The QIOs' full cohort of 970 HQIP projects could not be reviewed in the 10-month time frame available, but two topics were chosen: the management of warfarin or aspirin in patients with atrial fibrillation and the management of community-acquired pneumonia. FINDINGS: Analyses were limited to the 49 of the 68 projects that had progressed to the "improvement plan implemented" stage. However, only 39 of these 49 projects had information on outcomes, organization changes, and/or changes in process of care--and only 20 of the 49 had moved beyond the "improvement plan implemented" phase. Feedback of data led hospitals collaborating on improvement projects to revise or create processes of care. DISCUSSION: Although the assessment is the most comprehensive of its type to date, it should be viewed as a pilot study of some of the methods that could be incorporated in a more extensive and rigorous future evaluation of the impact of the HCQIP projects. Specific recommendations include random sampling of HCQIP projects across all clinical areas, conducting both prospective and retrospective assessments, developing uniform process and outcome program impact measures, and developing sustainable, ongoing automated data abstraction and analysis systems.

[New physician reimbursement guidelines and private health insurance. I. Changes in general liquidation regulations]. / Neue GOA und private Krankenversicherung. I. Anderungen der allgemeinen Liquidationsvorschriften.

In Germany, physicians' charges for the treatment of private patients have to be based on a fee-for-service schedule that is established by law. Every few years medical progress and changes of economic and legal conditions require major amendments. The latest adjustment reduces the accounts for laboratory tests and advanced imaging techniques. Further regulations concern the better information of patients about treatment costs and a reduced upper limit of fees for in-patient procedures not performed by the head of the department himself. For private insurers it is a challenge to identify the quite frequent medical accounts which are not in accordance with the complex fee schedule.

Stimulated duodenal/bile juice aspiration for diagnosis of enteric pathogens in HIV-infected patients.

Gastrointestinal and biliary abnormalities are common in the acquired immunodeficiency syndrome. Although obviously related to opportunistic infections in many cases, often no infectious agent can be identified. The specific diagnosis depends on invasive methods such as endoscopic retrograde cholangiography and liver histology. To evaluate an alternative and less invasive first-line approach, we conducted a prospective study of microscopic examination of aspirated duodenal/bile juice, to try to identify microbial causes of human immunodeficiency virus (HIV)-related gastrointestinal and biliary tract disease. Sixty-four HIV-infected patients underwent upper gastrointestinal endoscopy with biopsies from the esophagus, stomach, and duodenum, and aspiration of stimulated duodenal/bile juice. Biopsies, duodenal/bile juice, and stool samples were examined for enteric pathogens. Twenty-seven intestinal infections were found in 22 of the 64 patients (34%), 12 (44%) of which were diagnosed by duodenal/bile juice examination. Seven of the 27 infections (26%) were diagnosed exclusively in duodenal/bile juice, whereas 5 were found in biopsies or stool samples as well. Twenty infections (74%) were demonstrated in intestinal biopsies and/or stool samples, 15 without any positive result in duodenal/bile juice. The proportion of patients with elevated alkaline-phosphatase and gamma-glutamyl-transpeptidase activities was higher in patients with infectious agents detected in duodenal/bile juice (5 of 11, 45%), than in patients with infectious agents found exclusively in intestinal biopsies and/or stool samples (2 of 11, 18%). Analysis of duodenal/bile juice is a simple, rapid, and effective method for the detection of enteral pathogens in HIV-related gastrointestinal and biliary dysfunction. It increases the diagnostic yield above the results of intestinal biopsies and stool examinations alone.

[Endosonographic findings in the upper gastrointestinal tract in staging of malignant nodal and extranodal lymphomas]. / Endosonographische Befunde des oberen Gastrointestinaltraktes beim Staging maligner nodaler und extranodaler Lymphome.

Endoscopic ultrasound has not yet become a routine procedure for the diagnosis and therapy planning of malignant lymphomas, and it was always restricted to patients with gastric or bowel involvement. From 1990 to 1992, 33 endoscopic ultrasound investigations have been performed in 25 patients with malignant lymphomas at the Cologne University Hospital. In addition, 21 of these patients had other (conventional) diagnostic procedures at the same time serving as reference. Endoscopic ultrasound showed lymphomas in 16/21 patients, and no evidence of lymphomas in 5/21 patients. The referencial investigations together showed lymphomas in 17/21 patients, and no evidence of lymphomas in 4/21 patients. Therefore, sensitivity was 94%. 5 of the patients in addition had involvement of the upper gastrointestinal tract's wall, proven by referencial investigations, which was diagnosed correctly in all cases. The pathological lymph nodes appeared mostly as echopoor, rather sharply demarcated and homogeneous. Their size was 7 mm to 55 mm in diameter, median 11 mm. The different histological types of lymphomas could not be distinguished by means of these criteria. Endoscopic ultrasound allows a detailed view at the mediastinal and epigastrical lymph node stations and may give important informations for the staging of malignant lymphomas.

Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy.

We have previously shown that oral cisapride causes a dose-related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones; 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 +/- 7.6% of the initial value was observed at a mean 97.5 +/- 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 +/- 5.7% before ESWL treatment and to 145.0 +/- 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.

Induced gall-bladder contraction accelerates fragment clearance after extracorporeal shockwave lithotripsy.

At the end of extracorporeal shockwave lithotripsy (ESWL) gallstone fragments are dispersed throughout the gall-bladder. In this state they should be expelled more easily than when later sedimented to the gall-bladder fundus. Thus, a randomized study was performed to evaluate the clinical benefit of induced gall-bladder contraction after ESWL. One hundred and five patients with radiolucent gallstones (1-3 stones, diameter < or = 30 mm) were randomized to received either saline or an infusion of 0.2 micrograms/kg ceruletide. Stone clearance rates and incidence of biliary symptoms were recorded. Clearance rates at 6 weeks and 3 months after ESWL were significantly (P < 0.025) improved by the ceruletide infusion. This effect, resulting in shortened bile acid therapy, was limited to patients with small solitary stones and dependent on a good initial fragmentation. Major side effects attributable to ceruletide were not observed. These results suggest that induced gall-bladder contraction can be successfully applied as an adjuvant treatment in a subgroup of patients with small solitary gallstones.