[Ascites: pathophysiology, clinical aspects and therapeutic effectiveness].
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Biomedical subjects
Publications and source records attributed to E Frick.
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Cell-mediated cytotoxic reactions against myelin basic protein (MBP), encephalitogenic peptide, cerebrosides and gangliosides were studied in 165 MS cases. The cytotoxicity, which is detectable only in the autologous system, is mediated by T lymphocytes bearing antigens reactive with antibody OKT8. The cytotoxicity is highest during active MS regardless of whether it is relapsing or chronic progressive. During inactive MS cytotoxicity is significantly less and remains virtually unchanged at a low level over long periods. The degree of cytotoxicity is thus, predominantly, dependent on the activity stage of the disease. Further, there is a correlation with the severity of the clinical deficiencies. The pathogenetic significance of cytotoxic reactions can be recognized by the close correlation between the stage and course of MS, which can be demonstrated both statistically and individually.
In a Turkish couple presenting atypical precordial pain, muscle pain and a massive increase of creatine kinase during and one day after bicycle ergometry, suspicion of McArdle's disease was confirmed by a pathologic ischemic forearm worktest, a pathologic serial stimulation test and by pathologic glycogen content with lack of myophosphorylase activity on histochemical examination of thigh muscle tissue. Characteristic signs of McArdle's disease such as muscle weakness, muscle pain and muscle swelling, especially after exertion, were detected only after specific questioning of the patients. McArdle's disease was also detected by phosphor nuclear resonance in the two male children. Frequent consanguinity in the small isolated mountain village where the family originated explains why all four members of two generations are affected by the autosomal recessive disease.
On examination in the first weeks after onset of the disease, cell-mediated cytotoxicity against encephalitogenic peptide, myelin basic protein (MBP), cerebrosides and gangliosides was demonstrable in 32 (76%) of 42 patients with optic neuritis (ON). 14 patients with ON and concomitant neurological symptoms (ON/MS) had positive findings with all antigens, especially with the encephalitogenic peptide. The cytotoxic reactions against all antigens showed a close correlation with the course of ON: when the disease improved, the cytotoxicity decreased and became negative on average 4 months after ON onset. As previously reported, cell-mediated cytotoxicity against the above-mentioned antigens, especially the encephalitogenic peptide, may be considered as a pathogenetic factor in multiple sclerosis (MS). A positive reaction with this antigen in patients with ON only probably indicates the first manifestations of MS.
In multiple sclerosis (MS) different autoimmunological phenomena can be held responsible for the inflammatory demyelinating process. A cytotoxic reaction of lymphocytes against the encephalitogenic peptide of the myelin basic protein is assumed to be the primary factor; furthermore, demyelinating antibodies play an important part in the destruction of the myelin sheath. As can be identified at the acute stage of the disease, anomalies in the immunoregulation and the suppression of the control mechanism give additional indications towards the immunopathogenesis of MS. The cause of the demyelinating autoimmune process is unknown. According to epidemiological studies, a virus infection is the most likely etiology for MS.
Sera of 23 patients with Waldenström's macroglobulinaemia and six monoclonal IgM paraproteins, which had been isolated from these sera, were examined for reactivity against peripheral nerve tissue. Of these 23 patients, 12 had clinical signs of peripheral polyneuropathy (PN). Using an indirect immunofluorescence method, all sera and monoclonal IgM preparations reacted with peripheral nerve structures, displaying a distinct granular fluorescence pattern with anti-IgM sera. The Waldenström sera reacted mainly with structures at the border of the myelin sheath, as well as between myelin and axon, and occasionally with the axon itself. There was no difference between sera of patients with PN and those without. Negative results were obtained in a complement fixation assay. Of the 23 sera, 15 reacted in an antibody-dependent lymphocyte-mediated cytotoxicity reaction (ADLC) with peripheral nerve myelin, and to a much lesser extent with myelin basic protein from CNS. Five of the six isolated monoclonal IgM preparations also gave positive ADLC reactions. These results constitute additional evidence for an immunological mechanism in the pathogenesis of PN in Waldenström's macroglobulinaemia.
60 cases of orthopedic surgery and traumatology were treated 64 times altogether with an average dose of clindamycin of 3 X 300 mg/day. 40 patients were given clindamycin as preventive treatment. 12 patients were treated for acute infections of the locomotor system and other 8 patients 12 times for chronic osteitis. In the group having received preventive trqatment, infection occurred bu 1 out of 40 patients. As to the 12 cases of acute infections, 10 recovered, 1 improved and 1 patient got worse. Concerning the 12 treatments of 8 patients with chronic osteitis, in 1 case the inactivation of the infection was obtained. 9 cases showed significant improvement whereas in 2 cases an aggravation was noticed. In 5 patients the following side effects occurred: 2 cases of allergic exanthema, 2 cases of mild diarrhoe and 1 case of pyrosis. This study shows that clindamycin is an antibiotic with a broad field of application in orthopedic surgery.
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Azathioprine and its active metabolites can be detected in the cerebrospinal fluid (after i.v. injection). At a single dose of azathioprine maximum immunosuppressive activity occurs in the serum after 1 h and in the cerebrospinal fluid after about 4 h. Maximum immunosuppressive activity in human cerebrospinal fluid is about 12.5% of the equivalent serum level. A certain amount of time is needed for azathioprine and its metabolites to reach the cerebrospinal fluid where they remain for some time before passing into the serum, from where they are broken down. The findings are clinically important for the treatment of inflammatory nervous diseases, for example, multiple sclerosis, which are assumed to be of immunopathological origin.
In 79 of 100 patients with multiple sclerosis, serum antibodies of the IgG type were demonstrated which render normal lymphocytes cytotoxic against basic protein of myelin. In 11 cerebrospinal fluids which were tested the antibody was also found. The method used was the release of 51Cr from chicken erythrocytes coated with antigen. The antibody-dependent lymphocyte cytotoxicity is related to the degree of activity of the disease and not to the evolution of the disease or its course. As the disease worsens, the frequency of positive reactions is higher than in inactive stages. The immunological reaction is very specific for multiple sclerosis, in patients with other neurological disorders only 5% had positive findings. The antibody-dependent cytotoxicity of lymphocytes against basic protein of myelin may be attributed with a certain diagnostic significance. The reaction seems suitable for the supervision of the course of multiple sclerosis and to check the effect of therapeutic measures. The antibody-dependent lymphocyte cytotoxicity against basic protein of myelin is considered to be significant in the pathogenesis of multiple sclerosis.
During the long-term treatment with azathioprine of 79 patients suffering from MS there was a significant reduction in the relapse rate; the course of the disease was also favorabley influenced. In about one third of the patiens afflicted with the chronic progressive form of MS, there was no further progression. After conclusion of the treatment its favorable effect lasted for 1 to 2 years; then the disease worsened, and the relapse rate increased again. Treatment with antilymphocyte globulin and/or thoracic duct drainage in 18 patients led to impressive improvement or a stabilization of the neurological signs in those with a relapsing course. The chronic progressive course of MS was arrested in about two thirds of the patients. The effect of the treatment lasted from one to several years.
Cytotoxic antibodies to myelin can be demonstrated by the method of 51Cr-release from chick erythrocytes coated with myelin basic protein. The cytotoxic antibody is inactivated by heating to 56 degrees C and needs complement in order to exert its action. The antibody was determined as IgM and IgG. It has relative specifity and shows cross-reaction with other basic proteins. The cytotoxic antibody was found in only 8% of healthy persons. Patients with multiple sclerosis were positive in 87% of the cases and in acute cases in 94%. In other neurological diseases cytotoxic antibody was present in 64%. The occurrence of cytotoxic antibody to myelin protein is not specific for a particular neurological disorder, especially not for multiple sclerosis. Cytotoxic antibodies arise as a secondary phenomenon, they are not the cause of the disease involved. They appear to be suitable, however, to determine, in association with cellular immunological reactions against myelin which may be regarded as the "primary" immunological processes, the demyelination process in the multiple sclerosis focus.
Twenty patients with multiple sclerosis, in whom treatment with azathioprine and steroids had not altered the progression of the disease, were given additional treatment with either antilymphocyte globulin (ALG) (seven patients), thoracic duct drainage (TDD) (five patients) or a combination of both (eight patients). Four of the seven patients treated with the addition of ALG showed remarkable improvement which has lasted little improvement. In the eight patients receiving both had severe allergic reactions to ALG which prevented adequate dosage. TDD alone was performed in patients sensitive to ALG. These five patients showed little improvement. In the eight patients receiving both ALG and TDD there was marked improvement in four patients which has again lasted several years. The main side effect of ALG therapy is allergic reactions. Major infections or tumour formation did not occur in any patients.
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In chromosomes of peripheral lymphocytes of 35 patients with multiple sclerosis treated with azathioprine, antilymphocytic globulin or thoracic-duct drainage structural aberrations (breaks and gaps) were found at a significantly high rate. The aberration rates were increased in another ten untreated patients as well, but less so. Patients previously treated had a high aberration rate, too. The B- and C-chromosomes of patients treated with azathioprine were more frequently involved than those of control subjects. The terminal segment of the long arm of chromosome 1 was mostly affected in these patients, while in all groups there was an increase of aberrations in the centre of the long arm of the C-chromosome. The clinical significance of these chromosomal aberrations is not yet clear.
Damage to the spinal marrow by kyphoscoliosis shows a characteristic clinical syndrome: severe curvature of the vertebral column, first manifestation in the second decade or in the second half of life, at this time frequently associated with cardiac and circulatory failure, spinal symptoms often accentuated on the convex side of the scoliosis. Mechanical alteration of the spinal marrow and cardiovascular failure are considered to be pathogenetic factors. Kyphoscoliotic lesions of the bone marrow are rare and ought only to be diagnosed by exclusion. Conservative treatment consists of orthopedic measures and treatment of the heart and circulation. Operative decompression of the spine may be successful, but deterioration is possible after some years.
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