Search

There are at least two groups of issues connected with an impact of a realization of the "Human Genome Project": a) philosophical; b) ethical, which can be divided into four groups: 1) the influence of DNA technologies on everyday applications of bioethical principles; 2) ethical aspects of genetic diversity; 3) ethical aspects of genetic screening; 4) somatic and germ-cell gene therapy; Unlike essential philosophical issues practical realization of issues in question can be largely expressed as only revitalization of old ones and concerns: the principle of justice-equal access and priorities; protection of reproductive choices; disclosure to patients and to relatives at genetic risk (disclosure and exclusion tests); prenatal diagnosis for "mild to moderate" diseases with and without genetic indication-commercialization; insurance policy; non-directive and directive genetic counseling. Maybe there are regional and other differences, but in practice, the main ethical issues are likely to involve screening for genetic risk of common diseases of adult life e.g. hypertension, diabetes, gout, dyslipoproteinemia, genes for premature atherosclerosis, etc. because of the possible direct impact on a patient, an implication for life-insurance, employers and commercial exploitation.

The paper presents general therapeutic principles applied in systemic vasculitis. Several factors may help to contain the clinical activity, such as the location and extent of the inflammatory process affecting the vascular system, the ultimate narrowing of the vascular lumen with subsequent ischemia of the affected tissue and organ. Treatment of vasculitis involves besides glucocorticoids not only cytotoxic drugs (cyclophosphamide, chlorambucil, methotrexate), and immunomodulatory therapeutic agents with immunosuppressive action (cyclosporin A) but also other immunomodulatory drugs, as e.g. dialyzed homogenate of leukocytes (DHL), pentoxyphylline, hydrolytic enzymes, and monoclonal antibodies. The authors emphasize the importance of a complex approach in the management of systemic vasculitis. (Tab. 1, Ref. 36.).

Three different pathomorphological findings were presented in patients with seropositive borreliosis. Skin biopsy, cytology of joint synovial fluid and imprint cytology of bulbar conjunctiva were included. Skin vasculitis as well as pleocytosis of synovial fluid were found in accordance with literature, the inclusions in conjunctival imprint were unusual.

Serum beta-2-microglobulin was examined by radioimmunoassay in 103 patients with ankylosing spondylitis and 111 healthy blood-donors. Statistically significant difference between the group of patients and healthy individuals was found related to increased levels of this protein in patients with ankylosing spondylitis. Furthers correlation analysis of beta-2-microglobulin in patients with ankylosing spondylitis and chosen clinical and humoral parameters of the disease activity was performed. Positive, statistically significant correlation with erythrocyte sedimentation rate, plasmatic gamma globulins, duration of morning stiffness and global activity of the disease was proved. Higher levels of beta-2-microglobulin in patients with ankylosing spondylitis could be attributed to activation of monocyte macrophages system in subpopulation of cytotoxic T-lymphocytes, which might be the evidence of the involvement of cytotoxic-T cell mechanisms in the pathogenesis of this disease.

In our article is referred to the recognition of collagenosis in the demarcated whole district with 100,000 inhabitants. The occurrence of these diseases is lower than the occurrence of other rheumatic diseases. Our results as well as the observations of other authors confirm that the lupus erythematodes and the diffuse sclerodermia are not rare diseases even in our circumstances and with their evolution tendency they shorten the lives of the affected persons. The high recognition coefficient with large probability corresponds to the real incidence of these two diseases, which can be achieved only by an observation of many years and repeated controls of the correctness of the diagnosis.

Values of released enzymes from PMNL under resting conditions and after phagocytic stimulation in non-treated patients with gout were increased in comparison with healthy controls and hyperuricemic patients without joint involvement. Allopurinol, given to gout-patients for 3 weeks, had an inhibitory effect on PMNL lysosomal enzyme release from which was also observable after stimulation by opsonized zymosan. Similar results were obtained in experiments in vitro. The 1 hr preincubation of isolated polymorphonuclear leukocytes with allopurinol in concentrations from 0.01 mM-1 mM resulted in a dose-dependent decrease of enzymes released into extracellular space.

The anti-hyperuricemic effect of a daily doses of 100 mg of the normurat (Benzbromaron) was studied in 25 patients with gout. This agent leads to a rapid decrease to normal values of the elevated serum uric acid level. Within one week of discontinuation of the drug the serum urate levels rose to the initial pathological value. For some of the patients it was possible to keep the uric acid level within the normal range by administration of 50 mg of Benzbromaron daily or 100 mg every second day. The tolerance of the preparation was good and during the 4--6 months' long therapeutic trial there were no severe side effects.

The authors investigated the incidence of antibodies against Klebsiella pneumoniae and E. coli in a group of patients with ankylosing spondylitis and in a group of healthy controls in all main immunoglobulin classes. The results revealed that in patients with ankylosing spondylitis there is a significantly higher incidence of specific antibodies of class IgA against Klebsiella pneumoniae and E. coli. This supports the thesis on the aetiopathogenetic interrelationship between enteric bacteria and the development of ankylosing spondylitis.

It is reported on five cases of Weber-Christian's syndrome which were observed in our institute during the last years due to difficulties involving motion organs. In three of the cases short-term arthritis was found and in one of the cases erosion arthritis of rheumatoid type was found, too. As far as the last case is concerned detailed information on the system manifestation of the patient is given; the disease started in her young days with regular relapses and visceral manifestation. At the same time typical morphologic changes in the subcutaneous fatty tissue and in the liver as well as clinical findings of diabetes, pericarditis and focal myocarditis were observed which proved a general disorder of the lipid metabolism.

Serum uric acid levels were investigated in a series of 1715 subjects. Of these 596 were patients suffering from inflammatory rheumatic disorders, 162 patients with gout, 236 with osteoarthrosis and 79 with systemic lupus erythematosus or diffuse scleroderma. 642 healthy subjects completed the series. On analyzing the results, very high uricemia values were found in patients with gout. Increased average uricemia values were observed in patients with psoriatic arthritis and diffuse connective tissue disorders (systemic lupus erythematosus and diffuse scleroderma). Hyperuricemia was found in psoriatic arthritis, rheumatoid arthritis, and in nosologic units classified under diffuse connective tissue disorders in 5.6 to 10.1% of patients. In the healthy subjects examined, hyperuricemia was recorded in 3.8% of cases.

A retrospective analysis of the pharmacotherapy used in 100 patients during their illness was performed. The method was that of a standardized interview based on a questionnaire. Analysis of the data showed that salicylates still dominate among the first-line antirheumatic drugs, but are gradually being replaced by newer antirheumatic agents. A large number of patients received drugs belonging to the group of pyrazolidine compounds. Basic therapy primarily consisted of chrysotherapy; therapy with antimalarials had to be discontinued due to side effects in a high percentage of cases. An interesting finding is the high number of patients treated in the long term with glucocorticoids with apparently good tolerance.

In a prospective study (1961-1972) the incidence of rheumatic fever (RF), development of rheumatic heart disease (RHD) and penicillin prophylaxis efficacy were investigated in 300 000 children and 70 000 adults. Only patients whose index attack met the modified Jones' criteria were included; all were enrolled in a prophylaxis programme (i. m. benzathine-penicillin). The RF incidence decreased from an initial 61.2 attacks per 100 000 in children and 42.9 in adults to below 10 by 1969 and remained low thereafter. In total, 541 children (209 with carditis) and 176 adults (108 with carditis) were followed up for 5.5 years (average) after an index attack. At final examination, no valvular involvement was detected where previous attacks had been without clinical carditis. Patients studied from time of the primary attack with carditis (211) had a very favorable prognosis: only up to 3.5% had developed a moderate to severe heart lesion by the end of the study. However, of 68 adult patients followed up only from the time of recurrence with carditis and often having had a prolonged rheumatic history: 23.5% had a moderate to severe heart lesion and a further 20.6% had died of RHD by the end of the study. Prophylaxis efficacy calculated as a cumulative attack-recurrence rate per 100 patients and over a 5-year interval was 2.72 in protected as against 64.75 in unprotected children (mostly failing to comply with prophylaxis); in adults, the respective values were 1.3 and 24.92. The prevalence of serious residual RHD may be expected to decrease substantially in the future, starting with the younger age groups.