[Scientific raisins from 125 years SMW (Swiss Medical Weekly). Pseudohyperkalemia in thrombocytosis. 1960].
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Biomedical subjects
Publications and source records attributed to P G Frick.
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A material of 87 patients who underwent cardiac surgery for active infective endocarditis from 1975 to 1987 is analyzed retrospectively. 91 emergency operations were performed in 19 women and 68 men with a mean age of 48 years. 72 native valves and 19 prosthetic valves were involved. Streptococci (41%) and staphylococci (27%) were the most frequent bacteriological isolates, whereas 19% of the cultures remained negative. Heart failure (52%), embolism (21%), uncontrolled infection (11%), prosthetic valve endocarditis (10%), atrioventricular block (4%) and ventricular septal defect (2%) were the indications for surgery an average of 22 days after diagnosis. 17 patients (19%) died, 9 during hospitalization from heart failure or septicemia and 8 in the later course. 16 patients required reoperation for valvular incompetence (5), paravalvular leak (4) or prosthesis infection (7). Five relapses (5.5%) and two reinfections (2.5%) were treated surgically while two reinfections responded to medical therapy alone. Postoperatively, 34 patients (39%) suffered severe complications such as neurological deficits, prosthetic valve endocarditis or anticoagulant haemorrhage. After a mean observation period of 52 months (range 1-147 months) 64 (91%) of the surviving patients were in NYHA classes I + II and 6 (9%) in NYHA classes III + IV.
Clinical and serological data in 5 cases of autoimmune hemolysis following therapy with Catergen are reported and compared to the data in similar literature reports. The main argument in favour of Catergen as causative agent in our 5 cases was rapid remission of hemolysis within 2 1/2 to 10 weeks of withdrawing Catergen treatment. Besides causing hemolysis mediated by drug dependent antibodies, long term treatment with Catergen may induce formation of IgG autoantibodies against red blood cells with or without overt hemolysis.
In two randomized double-blind studies perioperative bleeding complications and thromboembolic events were assessed in 189 patients (pts) undergoing elective visceral surgery after subcutaneous administration of a low molecular weight (LMW) heparin fragment (KABI fragment 2165) or unfractionated (UF) heparin. The first study comparing 1 X 7'500 anti-factor Xa IU LMW heparin daily with 2 X 5'000 IU UF heparin was interrupted because of excessive bleeding complications (LMW heparin: 11/23 pts, UF heparin: 2/20 pts, p less than 0.01). In the second study (146 pts) the dose of LMW heparin was reduced to 1 X 2'500 anti-factor Xa IU. Bleeding complications (LMW heparin: 14.9%, UF heparin: 15.3%) and thromboembolic events (LMW heparin: 2.86%, UF heparin: 2.94%) were equal among the two groups. 2'500 anti-factor Xa IU/day of this LMW heparin fragment, corresponding to 15 mg/day, is the lowest dose of a LMW heparin used in a randomized clinical trial and was found to be a safe and efficient regimen in perioperative thrombosis prophylaxis. An advantage of LMW heparin over UF heparin is its once daily administration.
Seven cases of agranulocytosis and two of liver damage that were probably due to amodiaquine treatment were studied. In five cases agranulocytosis was combined with liver damage, and in one case of primary liver damage moderate neutropenia was present. Three patients died. High total doses or prolonged duration of treatment, or both, appear to favour the occurrence of these reactions. The clustering of five of the seven cases of agranulocytosis within six months in one medical centre indicates that the risk to benefit ratio of amodiaquine for malaria prophylaxis should be re-evaluated.
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The potential of ketoconazole prophylaxis to antagonize the activity of amphotericin B against aspergilli was investigated in vitro and in neutropenic mice. Exposure of Aspergillus fumigatus (six strains) and of Aspergillus flavus or Aspergillus niger to ketoconazole resulted in a uniform increase of the minimal fungicidal activity of amphotericin B, from 0.15-0.63 mg/liter to greater than 2.5 mg/liter in a microwell assay. To test the relevance of this antagonism in vivo, we challenged neutropenic mice iv with a lethal dose of conidia from two strains of A. fumigatus and then treated the mice first with ketoconazole and then with amphotericin B or amphotericin B plus ketoconazole. Pretreatment with ketoconazole for 48 hr completely abolished the protective effect of a subsequent therapy with amphotericin B, whether ketoconazole therapy was stopped (P less than .001) or not (P less than .001). Ketoconazole given alone had no significant effect on survival. Our data show that ketoconazole not only antagonized the fungicidal activity of amphotericin B in vitro but also abolished in vivo the protective effect of the only drug shown to be useful in the therapy of aspergillosis. The clinical importance of this antagonism, which is not limited to Aspergilli in vitro, requires careful consideration before ketoconazole prophylaxis can be recommended for patients at high risk of developing invasive opportunistic fungal infections.
Two patients with polycythemia vera received intravenously an accidental tenfold overdosage of radiophosphorus therapy (60 and 50 mCi 32P, respectively). In both patients, the occurrence of hemorrhagic complications 3 wk after the 32P medication led to detection of the error and referral to our hospital. Upon admission they showed an agranulocytosis, severe thrombocytopenia, and bone marrow aplasia. In both cases, spontaneous recovery of the hematopoiesis was observed from day 40 posttreatment onward. In one patient, a slow but ultimately complete normalization of blood counts and marrow morphology took place, whereas in the other, a mild thrombocytopenia persists. Nearly 5 yr after the accidental overdosage, both patients are clinically well. Symptoms of polycythemia vera have not reappeared up to now. Attempts were made to evaluate the radiation dose absorbed by the bone marrow. In the first patient, the daily 32P excretion was determined from day 22 to day 60, whereas in the other patient a whole body count was performed on day 78 after administration. From these results, an approximate cumulative bone marrow dose of 10 Sv (1000 rem) could be calculated.
A randomized study was performed in 54 thrombocytopenic patients with acute leukemia. Alloimmunization of recipients of random multiple-donor platelet concentrates (MD group) was compared to that of patients receiving random single-donor platelets (SD group). In the SD patients, formation of alloantibodies (mostly anti-HLA) occurred less frequently (p less than 0.002), after a longer time period (p less than 0.002), and after a higher number of transfusions (p less than 0.005) as compared to MD patients. SD patients also became refractory to random platelets less frequently (p less than 0.005), after a longer time period, and after a higher number of transfusions (p less than 0.02). In SD patients, the increments after the first and the last transfusion were in the same range, whereas in MD patients, the 1-hr (p less than 0.001) and the 24-hr (p less than 0.025) increments decreased from the first to the last transfusion. Thus, the use of random SD platelet transfusions postponed alloimmunization.
A female patient is described who developed skin and subcutaneous fat necrosis on two occasions after intake of acenocoumarol. Several months later identical skin changes occurred during an episode of cholestasis associated with a prolongation of the prothrombin time to an extent comparable with therapeutic anticoagulation; intake of oral anticoagulants could be excluded. This association gives new insights in the pathogenetic mechanisms responsible for the so-called coumarin necrosis and indicates that it may be not due to drug toxicity or allergy.
A 26-year-old man with severe aplastic anemia was treated with high-dose Cyclophosphamide followed by the infusion of bone marrow cells from his HLA-identical sister. After initial intake of the graft, rejection ensued by day 46 which was followed by a permanent complete aplasia. After 4 months, bone marrow retransplantation with the same donor was attempted after a more intensive conditioning regimen. This led to permanent engraftment with rapid normalization of the blood counts lasting now for over 12 months. The patient has since remained in excellent clinical condition without signs of graft-versus-host disease.
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