Biomedical subjects
Publications and source records attributed to W Stangel.
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A 49-year-old previously healthy man fell gravely ill after repeatedly eating the mushroom Paxillus involutus. Haemolysis and circulatory shock caused acute renal failure, acute respiratory failure and disseminated intravascular coagulation. The patient died three-and-a-half days after the mushroom meal in protracted shock. In addition to the signs of haemolysis, post-mortem examination revealed signs of intravascular coagulopathy in lungs, kidneys, adrenals, myocardium, liver and spleen. There were also extensive fat emboli to both lungs. An IgG antibody against paxillus involutus extract was demonstrated in the patient's serum. The immunological reaction pattern suggests primarily the formation of an immune complex, which secondarily attaches itself to the erythrocyte surface and causes intravascular haemolysis by activation of the complement chain. In the first instance the diagnosis is made from anamnestic data. In addition to adequate treatment of circulatory shock, immediate plasma separation could provide a chance of effective treatment.
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Electron microscopy (thin sections and freeze-fracture replicas) was performed on the bone marrow of ten patients with Polycythemia vera prior to any treatment. In addition to a hyperplasia of all three cell lineages and the sinuses, atypias were observed in the maturing erythroblasts. These aberrations of normal development consisted mainly of deep invaginations of the nuclear envelope in proerythroblasts and conspicuous nuclear clefts in erythro- and normoblasts. In comparison with similar changes in dyserythropoietic and aplastic anemia as well as leukemia these alterations are discussed in connection with disturbances of DNA synthesis. Further atypias involved megakaryopoiesis which displayed microforms probably as an evidence for maturation arrest. These ultrastructural abnormalities and their morphological features of a neoplastic proliferation of all three cell lineages in Polycythemia vera are in good agreement with the new concept of a transformation of a pluripotent stem cell with clonal character.
In the continuous cell separation (Aminco) the temperature of the extracorporal blood is diminished by 9.3 degrees C. The calculated cooling of the intracardiac blood of 0.1 degrees C does not lead to an irregular cardiac rhythm. The donor only needs 0.339 kcal/min to rewarm the blood. It is necessary to rewarm the blood before retransfusion only if you have proved evidence of coldness antibodies with an extremely wide amplitude of temperature.
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Thrombocyte yields up to 1,4 X 10(11) per litre of separated whole blood were obtained using centrifuge speed up to 2000 RPM. With increasing speed, higher platelet concentrations in the thrombocyte zone were accompanied by a progressive decline of thrombocyte counts in the plasma zone, whereas the thrombocyte contamination in the erythrocyte zone remained unchanged. Taking into account both high extraction efficiency and good preservation of platelet function as measured by Breddin's spreading test, optimal conditions for thrombophoresis with the Aminco Celltrifuge have been obtained at 1600 RPM. Since repeated separation of the donor's blood resulted in a rising number of platelets with impaired spreading capacity, the total blood flow should be limited to the blood volume of the donor.
The separation of approximately 75% of the platelets present in circulation and thrombocyte pool in healthy adult donors by continuous flow centrifugation lowers the mean thrombocyte concentration to 140 +/- 28 X 10(3)/microliter. A dangerous thrombocytopenia can not occur since the platelet count in the reinfused erythrocyte zone remains at around 88 X 10(3)/microliter. The reactive rise of the platelet count after separation, the extend of which depended on the total amount of harvested thrombocytes, reached values around 277 X 10(3)/microliter. The total thrombocyte yield exceeded the calculated yield by 30%, indicating emptying of a quiescent thrombocyte pool. Thrombopoietin activity could be demonstrated in donors' plasma at 12 and 24 hours after thrombophoresis.
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The kinetic of 51Cr-labelled autologeous and heterologeous thrombocytes was studied in 12 healthy volunteers. The mean recovery value was 63% (SX = +/- 15%). The survival times (t50% and t10%) were determined as 94 hrs. (SX = +/- 11 hrs.) and as 202 hrs. (SX = +/- 13 hrs.) respectively. The "excess counts" over spleen and liver were measured and the spleen to liver ratio calculated. In every parameter investigated no significant difference between autologeous and heterologeous labelled thrombocytes could be found. The "excess counts" over spleen and liver were calculated on the basis of the radioactivity of blood and of the heart surface area. The values obtained from the blood radioactivity calculations showed significant lower variation coefficients than the corresponding values derived from the heart measurements.
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Multidrug resistance refers to a complex cellular phenotype, the hallmark of which is cross-resistance to multiple drugs, for example, chemotherapeutic agents, that are unrelated to the selecting agent in structure, cellular target, and mode of action. The expression of this multidrug resistance is connected with the overexpression of P-glycoprotein. By applying the method of immunocytochemical assay, we have demonstrated the appearance of the multidrug-resistant phenotype (P-glycoprotein+ cells, multidrug-resistant cells) in mononuclear cells of the peripheral blood from 32/49 patients receiving triple-drug (azathioprine, steroids, cyclosporine) immunosuppressive therapy after heart transplantation. In the group of patients showing not only the presence of cells with multidrug-resistant phenotype in the peripheral blood, but also a significant increase in the number of these cells during the interval of observation (0 to 767 days)-16/32/49 cases--a significantly increased incidence of acute rejection episodes could be demonstrated. This supports the hypothesis of a possible existence of a therapy-resistant form of acute rejection, with an involvement of mechanisms of multidrug-resistance playing a role in its causal development.
A set of early diagnostic (ED) criteria comprising clinical data, ESR, radiological spinal signs, and the risk factor HLA B27 was evaluated after 5 and 10 years in a follow-up of 54 patients with an initial diagnosis of possible ankylosing spondylitis (AS). After 10 years 32 patients (59%) had developed definite AS according to the New York criteria, 10 individuals (19%) had possible or undifferentiated spondylarthropathy (SA), whereas in 12 patients (22%) other diagnoses were stated. ED criteria had a high discriminatory significance for the development of AS after 5 and 10 years (P less than 0.005, P less than 0.001 respectively). In this respect they were more valuable than B27 determination alone (P less than 0.01) or the ED criteria without HLA B27 (P less than 0.05). Furthermore, patients with still possible or undifferentiated SA had a higher mean score at the first examination than individuals with other final diagnosis (P less than 0.05). Thus, the ED criteria were useful for the identification of patients developing definite AS and of individuals in the AS related group of possible or undifferentiated SA.
A family study was performed in 24 members of a Turkish sibship with familial Mediterranean fever (FMF) with 5 patients affected in 3 generations. The well-known autosomal-recessive inheritance of the disease was masked by a pseudodominant appearance, reflecting the striking frequency of congenial marriages. The immunogenetic investigation excluded a linkage between the expression of the disease and the HLA system. The arthritis of FMF was characterized typically by monarticular attacks in large joints of the lower limb. Frequently this manifestation led to diagnostic problems, particularly at the onset of the disease. No patient presented the clinical or radiological signs of sacroileitis. An observation of the disease process up to 3 years showed a benign prognosis of FMF-arthritis in 3 of 4 patients. Neither long-lasting functional impairment nor radiological signs of erosion had to be recognized. One patient suffered from a necrosis of the femoral head, possibly caused by the recurrent inflammation of the hip joint. Laboratory findings reflected the clinical picture of relapsing acute inflammation in an uncharacteristic manner. Their diagnostic significance exists mainly for the exclusion of other diseases.