[Back pain: guidelines for drug therapy. Utilize the therapeutic spectrum]. / Rückenschmerzen: Leitlinien der medikamentösen Therapie. Nutzen Sie das Therapiespektrum.

For the treatment of back pain, behavioral modification, pharmacotherapy, non-pharmacological conservative treatment and surgical procedures are available. Systemic and metabolic disorders require specific treatment. Medication that may be considered includes non-opioid analgesics with or without an antiphlogistic action, opioid analgesics, muscle relaxants and antidepressants. The choice of substance(s) will depend on the pathophysiology and the duration of the pain condition. In the case of acute pain with an inflammatory component, NSAIDs are the drugs of first choice. However, prolonged administration carries a risk of gastrointestinal and renal complications. Muscle relaxants may be useful adjuvants for a limited time. For myofascial pain, flupirtine is to be recommended because of its analgetic and muscle-tone-normalizing actions. Local anesthetic infiltration or nerve blocks are useful in blocking nociception with its pathophysiological sequelae. For chronic back pain, opioids and some antidepressants have a more favorable benefit-risk profile than NSAIDs.

[The established rheumatologist in the tension field between health care deficits and cost control in public health]. / Der niedergelassene Rheumatologe im Spannungsfeld zwischen Versorgungsdefiziten und Kostensenkung im Gesundheitswesen.

The outpatient treatment of rheumatoid patients in Germany depends on certain conditions. Rheumatologists in Germany need to cooperate much more with hospitals specialized in this field than other subspecialties of Internal Medicine. Because of historical reasons many other physicians such as orthopedics, internists, general practitioners participate in this field in contrast to our neighbours in the western hemisphere, where rheumatology is solely covered by rheumatologists. It is therefore conceivable to calculate a rheumatologists/population relation of appr. 1:200,000 and not less than this figure. Starting a business as rheumatologist needs certain conditions, which are specified. One major challenge will be the new law directing out-patient treatment in Germany (Gesundheitskontrollgesetz). It forces the doctor to relate his work to a more financial background with various restrictions and regulations. In this context our goal(s) must be the institution of a specified position in the "Gebührenordnung", to pay for our intense and time consuming efforts to treat our patients.

A rheumatologist's viewpoint.

Attitudes to prescribing anti-inflammatory drugs have changed considerably over the last 25 years and there is now a recognition of the need to balance effectiveness with reduced risks of serious adverse reactions. Such serious side-effects often involve the upper gastrointestinal tract, and there are differences between anti-inflammatory drugs in the frequency with which they cause significant problems at this site. Anti-inflammatory drugs with a lesser propensity to cause gastrointestinal reactions may have an advantage. Several risk factors may be important for upper gastrointestinal side-effects including sex, age, history of dyspepsia, other diseases and the type of arthritis. Results from post-marketing surveillance studies of nabumetone in the United Kingdom and the Federal Republic of Germany showed that although patients with a previous history of dyspepsia were more likely to stop the drug due to an adverse reaction, the majority continued without any problem. Interestingly, patients with rheumatoid arthritis were more likely to stop therapy due to side-effects, though it was not clear if this was due to their disease or to multi-morbidity. Strategies are needed when prescribing anti-inflammatory drugs which take into account the type of patient, their disease, and the best drug. In many instances this could be nabumetone.

German drug monitoring studies with nabumetone.

Although randomised controlled comparative trials concerning the efficacy of the drug tested can produce reliable results in a limited number of selected patient groups, drug monitoring studies involving 10,000 patients or more are the methods of choice to detect rare adverse events. The aim of this drug monitoring study was to evaluate the efficacy and safety of dispersible nabumetone tablets. 8865 patients (46.2% male, 53.5% female, mean age 55 years, range 14.95) were involved in the investigation carried out by 1172 general practitioners. The disease indications comprised osteoarthritis (69.8%), soft-tissue rheumatism (11.3%), rheumatoid arthritis (9.9%) and soft tissue injuries (7.7%). Most of the patients (67.3%) received a daily dose of nabumetone 1 g for up to 6 weeks. Efficacy was evaluated at baseline, and after 1 week, 3 weeks and 6 weeks of treatment. With regard to global efficacy, overall improvement (symptoms resolved or markedly improved) was assessed in 82% of the patients. Elimination or at least significant improvement of pain on movement occurred in 95%, pain on pressure in 90% and pain at rest in 89% of the patients with symptoms. In relation to swelling, morning stiffness and joint mobility, elimination or at least significant improvement occurred in 79%, 80% and 82% of patients, respectively. 1846 patients (20.8%) had frequent periods of NSAID-related symptoms before treatment with nabumetone. A total of 1174 adverse events occurred in 850 patients (9.6%), most comprising minor gastrointestinal complaints. Considering that at least 25,000 patients have been documented in 2 German drug monitoring studies, it is therefore unlikely that any unexpected side effects will occur in the future. Consequently, nabumetone can be classified as an effective and safe NSAID.

Phenotypic heterogeneity of cerebrospinal fluid-derived HIV-specific and HLA-restricted cytotoxic T-cell clones.

A variety of clinical syndromes, including AIDS and neurological disorders, may follow as a consequence of infection with the human immunodeficiency virus type 1 (HIV-1). It is not yet clear, however, to what extent the destruction of lymphocytes and neural cells associated with these conditions is caused by adverse immune responses to HIV-1 or how much is due to cytopathic effects of the virus itself. Here we document the existence of HLA-restricted, HIV-1-specific cytotoxic T lymphocytes in the cerebrospinal fluid of two AIDS patients manifesting neurologic disorders. These cytotoxic T lymphocytes showed dual specificity, recognizing target cells coated with purified HIV-1 envelope glycoprotein (gp 120) or inactivated HIV-1 in the context of HLA antigens. Cytotoxic T-cell clones derived from one of the AIDS patients revealed restriction specificities representing both HLA class I and HLA class II antigens. Considerable phenotypic heterogeneity was observed amongst these clones, some expressing conventional combinations of cytotoxic T-cell surface markers, and others displaying unusual phenotypes. The presence of HIV-specific cytotoxic T lymphocytes in AIDS patients, and in particular in their cerebrospinal fluid, suggests that these cytotoxic effectors may participate in the lymphoid cell and/or neurologic damage observed in such patients.

[Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo-controlled study of 119 patients]. / Immunmodulierende Therapie der chronischen Polyarthritis mit Thymopentin. Eine multizentrische placebokontrollierte Studie an 119 Patienten.

In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects.

[Therapy of seronegative oligoarthritis with salazopyrine]. / Die Therapie seronegativer Oligoarthritiden mit Salazopyrin.

In an open, controlled study we treated 55 patients suffering of psoriatic arthritis (PsA), 29 patients suffering of Bechterew's disease (MB) and 16 patients with Reiter's syndrome with Salazopyrin at a daily dosage of 2000 mg. We monitored the following criteria of activity: duration of morning stiffness, joint index, global well being scored by the patient and erythrocyte sedimentation rate. All these criteria improved during the treatment; there was a profound improvement in the RS group, whereas the MB group showed only a slight improvement; the PsA group ended between this two extremes. The effect of the drug appeared between week 5 and 15 of treatment. 21% of all patients had to discontinue the treatment because of severe side effects; this figure correlates with the percentages given in the literature. Most of these side effects appeared from week 3 to week 7 of treatment; after week 15 none of the patients had to discontinue the medication of because of severe side effects.

Reduction of infection frequency by intravenous gammaglobulins during intensive induction therapy for small cell carcinoma of the lung.

Thirty-two patients with small cell carcinoma of the lung received intensive induction chemoradiotherapy. In a randomized prospective study, we compared the outcome of patients who received 30 g immunoglobulin i.v. divided into three doses per therapy course for infection prophylaxis (Group A) with patients undergoing the same anti-tumor therapy (Group B). All patients were prospectively randomized to one of two groups in order to evaluate the role of intravenous immunoglobulin therapy for infection prophylaxis. Group A received 30 g intravenous immunoglobulin during each course of chemotherapy. Group B was a control group that received identical chemoradiotherapy but did not receive any immunoglobulin therapy. All patients had a severely impaired cellular immune response. IgG serum concentrations were significantly higher in group A. Patients who received intravenous immunoglobulin had significantly fewer infections during the entire treatment period than patients who did not receive prophylactic treatment.

[Heart involvement in progressive systemic sclerosis (generalized scleroderma)]. / Herzbeteiligung bei der progressiven Systemsklerose (generalisierten Sklerodermie).

17 patients with progressive systemic sclerosis were examined for cardiac involvement using standard ECG, chest X-ray, 24-h Holter ECG, and echocardiography. The control groups consisted of 7 patients with mixed connective tissue disease, 10 patients with systemic lupus erythematosus, and 10 patients with rheumatoid arthritis. The results disclosed a cardiac involvement of 70% using all 4 methods, which is more than is reported in the literature. The data also show that all 4 methods are necessary to diagnose the cardiac involvement. Conduction and rhythm disorders especially are more frequent than in other collagen vascular diseases. The use of calcium channel blockers is discussed as a new therapeutic possibility.

Pigeon breeder's lung: association with HLA-DR 3.

52 symptomatic (SPB) and 64 asymptomatic (APB) pigeon breeders were investigated for the HLA-A, -B, -C, -DR; C2, C3, C4 and Bf systems, and C3, C4 and factor B serum concentrations. HLA-DR3 and Bf S frequencies were significantly higher in the SPB than the APB group. Mean factor B concentrations were lower in the SPB than in the APB group. A positive two-way association between HLA-DR3 and the disease was found. It is concluded that a gene or genes responsible for type III and IV allergic reactions leading to the disease is associated with HLA-DR3. The increase of Bf S allotype and low mean factor B concentrations, however, can be explained by the strong linkage disequilibrium between BfS and HLA-DR3.

Generation of cytolytic T-cell cultures displaying measles virus specificity and human histocompatibility leukocyte antigen restriction.

In the present study, peripheral blood lymphocytes from eight randomly selected, healthy, measles virus-seropositive donors were used to initiate and expand T-cell cultures during secondary immune response in vitro. Five of the donors yielded continuously growing T-cell cultures which showed reproducible strong lytic activities towards measles virus-infected autologous fibroblasts. Uninfected or herpes simplex virus-infected targets were weakly susceptible to these effectors. By contrast, T-cell cultures from three other seropositive donors expressed comparable lytic activities for measles virus- or herpes simplex virus-infected targets, but not for uninfected autologous targets. The five T-cell cytolytic cultures which revealed measles virus specificity also displayed human histocompatibility leukocyte antigen (HLA)-A and HLA-B restriction, i.e, were lytic for targets sharing HLA-A or HLA-B or both with them. Additionally, it was found that a monoclonal anti-HLA antibody (W6/32) could effectively block the measles virus-specific and HLA-A- and HLA-B-related lytic activities of these cytotoxic T-lymphocytes. The specificity of this blocking effect was reflected by the inefficacy of a monoclonal anti-HLA-DR antibody to block the cytotoxic T-lymphocyte-mediated lysis.