Biomedical subjects
Publications and source records attributed to N Thumb.
A short review on incidence, prevalence, possible causes and pathologic findings in sarcoidosis is given. Especially the symptomatology, differential diagnosis and therapy will be described. Finally some data on 10 patients with this syndrome will be presented.
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The drug therapy of osteoarthritis and mainly of the large joints consists in less severe cases in analgesic drugs. Nonsteroidal antirtheumatic drugs with their analgesic and antiinflammatory action are used in more severe cases. In elderly persons their side effects are more serious, therefore strict controls are important. Therapy with so-called chondroprotective substances is not yet established but the glycosaminoglycan-peptid and also the glucosaminosulfate may be able to slow down the arthrotic process. An additional therapeutic possibility are intraarticular injections of hyaluronic acid and the knee-lavage. A drug therapy in osteoarthritis should never be given as a single measure, but always in combination with physiotherapy and general measures like weight reduction or using a cane, etc.
Growth-hormones like Insulin-Like-Growth-Hormone-1 (IGF-1) and Tissue-Growth-Factor-beta (TGF-beta) and Cytokines IL-1, IL-6 and TGF-alpha play an important part in the homeostasis and also degradation of the articular cartilage. IL-1 stimulates the production of proteolytic enzymes and inhibits the synthesis of aggrecan and leads therefore to a degradation of the cartilage. TNF-alpha acts in a similar way, whereas the significance of IL-6 for chondrocytes is not yet fully understood. TGF-beta and IGF-1 in contrast have a positive influence on cartilage metabolism, f. ex. TGF-beta stimulates the synthesis of the natural occurring metalloproteinase-inhibitor (TIMP).
Bronchoalveolar lavage (BAL) was performed on 70 RA patients, 28 without extra-articular manifestations, nine with pulmonary involvement, 13 with sicca-syndrome, 20 with other extra-articular manifestations such as renal involvement, cutaneous vasculitis and rheumatoid nodules. Fifteen patients without rheumatic or pulmonary disease served as the control group. Compared with the control group RA patients showed a statistically significant increase of lymphocytes, especially of activated (DR+)T(CD3+)-helper (CD4+) cells, resulting in a significantly diminished percentage of alveolar macrophages, B(CD21+)-lymphocytes, T-suppressor (CD8+) cells and an increased CD4/CD8 ratio. This cell distribution pattern was more pronounced in RA patients with lung involvement with significant differences to the other RA patients with regard to lymphocytes, DR positive cells and CD4 positive/DR positive cells. It is concluded that these results indicate an altered balance of immunocompetent cells not only in the joints but also in the lung. The changes are more distinct if local manifestations can be diagnosed clinically.
The frequency of occurrence of Helicobacter pylori in the antral mucosa was investigated prospectively in a group of 66 patients (17 men, 49 women, mean age 58 +/- 8.4 years) who had been treated with nonsteroidal anti-rheumatic drugs and 33 controls (14 men, 19 women, mean age 60.7 +/- 6.6 years) who had not received these drugs. In the first group the indication for gastroscopy was ingestion of nonsteroidal antirheumatic drugs for at least 8 weeks, irrespective of dyspeptic symptoms (present in 25 patients), while in the second group the reason for endoscopy was either clinical symptoms (n = 18) or the presence of blood in the faeces. Helicobacter pylori was demonstrated by culture in 36 out of the 66 patients who had received nonsteroidal antirheumatics (54.5%); these comprised 24 out of 46 patients (52.2%) with chronic inactive gastritis and 12 out of 15 patients (80%) with chronic active gastritis. In the control group H. pylori was detected by culture in 22 out of 33 patients (66.7%); these included 11 out of 19 patients (57.9%) with chronic inactive gastritis and 11 out of 12 patients (91.7%) with chronic active gastritis. H. pylori was not demonstrated in any of the seven patients who had histologically normal gastric mucosa. In both groups there was significant correlation between demonstration of the microorganism and severity of inflammation. There is hence no evidence that nonsteroidal antirheumatic drugs have any influence on the colonisation of the antral mucosa by Helicobacter pylori.
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Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis.
Approximately a quarter of polyarthritis in the elderly is beginning with a single- or oligo-articular attack of big joints. The first attack of the shoulder joints is noticed especially in men. Most of the patients with rheumatoid arthritis in the elderly have a gradually progressive course. There is often showed a very high blood sedimentation rate (BSR); rheumatoid factor is rare. Generally there is a strongly marked osteoporosis. The success of therapy with disease modifying agents is comparable with that of younger patients with rheumatoid arthritis, but there is a smaller tolerance to gold and D-penicillamine. In some non-steroidal anti-rheumatic drugs a lower dosage is recommended.
The diagnosis of rheumatic diseases should follow a pattern of stages, the first comprising family case history, the case history of the patient and basic physical examinations. The second stage should include X-ray examination and basic or, if necessary, more extensive laboratory tests and simple synovia analysis. The third stage would then incorporate articular biopsy, arthroscopy, different biopsies outside the joint, isotope examination, electromyography, thermography, arthrosonography, computed tomography etc. Allowance should be made in this connection for the diagnostic criteria established by different specialist bodies and the different degrees of diagnostic safety involved. While computerized diagnostic systems for rheumatic diseases can be of great help to the GP, they will never be as successful as the experienced rheumatologist.
Numerous open and placebo-controlled trials have shown Auranofin, an oral gold salt, to be effective in the base-line treatment of rheumatoid arthritis. In comparative trials the drug was found to be somewhat less potent than sodium aurothiomalate. Whether it is equal or superior to other base-line antirheumatoids like D-penicillamine or antimalarials, can as yet not be established because of the small patient groups involved in the published trials. While adequately effective clinically, oral gold salts, like their parenteral counterparts, do not halt the radiological progression of rheumatoid lesions. Overall, Auranofin is much better tolerated than the parenteral gold salts, although soft feces are more commonly seen and diarrhea may occur occasionally. Skin rashes as well as proteinuria and thrombocytopenia have been reported in some instances so that, as during parenteral treatment, laboratory studies at regular intervals are mandatory. On account of its oral dosage form and its low side-effect rate Auranofin is a true alternative to conventional parenteral gold salt therapy.
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In 15 patients with inflammatory and degenerative joint disease the concentrations of lonazolac were measured in serum and synovial fluid at steady state conditions. The mean concentration in the synovial fluid in 14 patients was 0.275 microgram/ml, which was 48% of that in the serum. For the patients with inflammatory joint disease, the synovial fluid concentration of lonazolac was 61% of that in the serum whereas in degenerative joint disease it reached only 39%.
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Sixty-eight patients with urinary infection were allocated at random to receive treatment with either 500 mg ampicillin 4-times daily or a trimethoprim (250 mg)/sulfamethopyrazine (200 mg) combination given once daily after a double, loading dose on the first day. All patients complained of urinary symptoms and showed significant bacteriuria, E. coli being the pathogen most frequently recovered. Clinical and microbiological assessments were carried out on entry and, as a rule, after 3 to 4 days and 1 to 2 weeks of treatment. In the 35 patients receiving trimethoprim/sulfamethopyrazine, 40 (95%) of the 42 original infecting organisms were eradicated. In the 33 patients on ampicillin, the eradication rate was 32 (89%) out of 36 organisms. The course of urinary symptoms was similarly favourable in the two groups. Overall response was considered as 'excellent' or 'good' in 89% of the patients receiving the combination preparation and in 82% of those given ampicillin. Clinical and biological tolerance was satisfactory under both regimens. A longer follow-up control should confirm the value of the new combination in the treatment of urinary infections.
Non-steroidal antirheumatic drugs permit a nonspecific, symptomatic therapy of inflammatory rheumatic processes and may also be given for a limited period of time in patients with so-called activated osteoarthrosis. Their mode of action is a complex one. More recent knowledge on mediators in inflammation such as prostaglandins, leukotriens and oxygen radicals have brought new insights on the mode of action of non-steroidal antirheumatic drugs.
The functional capacity of 46 patients with rheumatoid arthritis was assessed by means of two systems of investigation. Three different questionnaires were used. One set of each was filled out by the patient himself; the other with the help of the occupational therapist. The results obtained were tested for their reliability. In addition they were also compared to the Ritchie-Index (method of simple measurement of disease activity) of thirty patients. The disability of each patient could be assessed with sufficient precision. A correlation to the Ritchie-Index was also registered.
By means of the exploration of patients suffering from an active, unequivocal rheumatoid arthritis it was possible to show the unequivocal, and antiinflammatory effect of 4-phenyl-1,2-diphenyl-3,5-pyrazolidinedione (feprazone, Zepelin). Moreover, it was documented that thermography is a very suitable medium to furnish proof of this effect and can be used to the advantage of the patients in clinical routine. The physiological processes of the production and distribution of heat must be taken into account to avoid false interpretation of thermograms.