C1q: a multifunctional ligand for a new immunoadsorption treatment.

C1q is a highly conserved protein with multiple functions involved in innate and adaptive immunity. It plays an important role in the activation of the classical pathway of the complement system to mediate the scavenging of infectious agents, apoptotic products, and immune complexes by the mononuclear phagocyte system (MPS). Exhibiting this function, C1q is able to bind various molecules (complexed IgG, IgM, fibrinogen, fibronectin, lipopolysaccharides, DNA, C-reactive protein [CRP], and viral proteins). Moreover, the collagen-like region of C1q is a target of autoantibodies. Immune complexes and anti-C1q autoantibodies are known to be involved in the pathogenesis of autoimmune diseases. Therefore, C1q is a promising candidate to extract waste material from the circulation. Following the development of the C1q immunoadsorbent, 8 patients with systemic lupus erythematosus (SLE) were treated in a first clinical trial. These preliminary results indicate that C1q immunoadsorption is a safe, compatible, and effective treatment for these patients.

[Pain treatment with dihydrocodeine slow release. Results of a post marketing surveillance study.]. / Schmerzbehandlung mit Dihydrocodein retard : Ergebnisse einer Anwendungsbeobachtung bei niedergelassenen Arzten.

Chronic pain requires chronic treatment. Dihydrocodeine retard (DHC) complies with the requirements for treatment of chronic pain: its sustained release formula provides pain relief for up to 12 h. Thus, taking two tablets of this preparation daily is sufficient to ensure continuous pain relief. Patients and methods The 309 physicians participating in the study treated a total of 1502 patients and provided more than 5000 reports containing data on pain relief and side effects. Treatment was performed according to the WHO principles for the analgesic treatment of cancer pain patients, i.e., doctors and patients were taught that two tablets are taken per day, one in the morning and one in the evening, irrespective of whether pain was present or not. Most of the data were derived from the first 4 weeks of treatment. Patients were selected at random. All had chronic pain, but the diagnosis was not a selection criterion. The patients had had prior treatment with various analgesic regimens, and in most cases drugs were administered at irregular intervals, i.e., on demand. About half of the patients (54%) suffered from pain related to the musculoskeletal system such as back pain, joint pain, polyarthritis. Twenty-four percent had cancer pain and 22% had pain caused by other sources, mostly neuropathic pain, including cases of severe postherpetic neuralgia. Most of the patients were older than 50 years; the average age in the patient population was 62 years. There were 816 women and 686 men. Patients assessment of analgesic treatment was performed before starting therapy with DHC (thus conferring to prior therapy) and after 1 and 2 weeks of treatment with the new drug. While only about 10% of the patients found their prior pain treatment excellent or good, nearly 80% rated the treatment with DHC as excellent or good and only 2% as bad.Severity of pain was assessed by the patients on a four-step verbal rating scale ranging from "no or little pain" to "extremely strong pain". At the time of admission to this post-marketing surveillance 51.5% of the patients suffered from very strong pain and 41% reported strong pain. Five percent had extremely strong pain and only 2.1% reported no or little pain. After 2 weeks of treatment with DHC, 54.5% had little or no pain, 29% suffered from strong pain, 7% from very strong, and 0.4% from extremely strong pain.Sleeping problems are known to be reported by patients with chronic pain. They often cannot sleep continuously for more than a few hours. Thus, the effect of DHC on sleep was evaluated. Before starting the new treatment only 8% of the patients were having uninterrupted sleep for 6 h or more, and more than 50% of the patients slept less than 3 h. During treatment with DHC 48% of the patients had more than 6 h of uninterrupted sleep and about 82% slept continuously for more than 3 h per night. Side effects About 20% of patients reported nausea at baseline (during previous treatment); vomiting was reported in 7.6%. These percentages did not change during the first week of treatment with sustained-release DHC and even decreased slowly during the next 3 weeks. The frequency of constipation increased from 14% at baseline to about 29.5% at the end of the second week of treatment with DHC with no change during the next four weeks. A total of 312 side effects were mentioned in 5308 reports delivered by the 1502 patients during the treatment with DHC (including multiple reports). The most frequent side effects were gastrointestinal (n=106), followed by symptoms related to the central nervous system such as dizziness, sedation, etc. (n=50), and non-specific symptoms such as indisposition (n=29). Other specific symptoms were rare and distributed over many different organ systems. Insummary, the findings of this post marketing surveillance study suggest that sustained-release dihydrocodeine is an effective and safe analgesic drug for the treatment of chronic pain of various causes.

Analgesic effects of dihydrocodeine and tramadol when administered either in the morning or evening.

The aim of the study was to investigate the analgesic effects of two opioids [dihydrocodeine (DHC) and tramadol] when administered either in the morning or evening. The experimental technique used is based on chemosomatosensory event-related potentials (CSSERPs) in response to painful chemical stimuli that are applied to the nasal mucosa. Eighteen healthy volunteers participated in the experiments. The study followed a controlled, randomized, double-blind, sixfold, cross-over design. Thus, each of the three medications (90 mg DHC, 50 mg tramadol, or placebo) was perorally administered to all subjects on different days at 08:00 or 20:00 h. Measurements were performed before and 60, 120, 240, and 360 min after administration of the medication. In addition to the assessment of CSSERP, subjects rated the intensity of the stimuli. Moreover, unspecific drug effects were monitored by means of acoustical event-related potentials and the subjects' performance in a video game. The results indicated that the painful intensity of the chemical stimuli strongly increased during evening sessions. In addition, both DHC and tramadol exerted stronger analgesic effects when administered in the evening. Thus, an inflexible scheme of prescription might produce either an increase of pain in the morning due to insufficient analgesia or the unnecessary overdosing of analgesics in the evening.