[Some advises to my house physician if I have one].
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Biomedical subjects
Publications and source records attributed to B Wadman.
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The effects of methimazole or betamethasone therapy on the TSH receptor antibody response to radioiodine therapy were compared in a prospective randomized study of 60 patients with hyperthyroidism due to Graves' disease. The patients were followed for 1 yr after treatment with 131I. Twenty-three patients received 131I alone, 17 were treated with methimazole for 2 months before and 3 months after 131I therapy, and 20 patients were treated with betamethasone for 3 weeks before and 4 weeks after 131I therapy. 131I induced a transient rise in the mean serum level of TSH receptor autoantibodies, measured as TSH binding inhibitory immunoglobulin (TBII), but in patients receiving methimazole treatment, no such rise occurred. In the betamethasone-treated patients, TBII increased similarly to that in patients treated with 131I alone. In addition, in patients given betamethasone, there was an early decrease in total serum immunoglobulin G, which persisted throughout the follow-up period. In the other 2 groups, no changes in total immunoglobulin G were found. The results demonstrate that in hyperthyroid Graves' disease, TBII production is influenced by therapy. Methimazole abolished the 131I-induced increase in TBII, whereas betamethasone did not have such an inhibitory effect.
Patients with newly diagnosed multiple myeloma were randomly allotted to an intermittent high-dose melphalan/prednisone (MP) treatment (120 patients) or a continuous low-dose melphalan (M) regimen (99 patients). The median observation time was 59 months (range 33-84). Response to therapy was obtained in 45% of the MP group and 31% of the M group (P less than 0.05). No significant difference in response with regard to clinical stage was noted. Median survival was 36 months in the MP group and 29 months in the M group. Survival was longer in stage I and II myeloma than in the stage III cases, at least in the MP group. The median and 5-yr survival rates in stages I and II were significantly better in the MP than in the M group. Response to therapy was associated with length of survival, median survival being 62 months in responding patients and 20 months in non-responders. The MP and M groups did not differ in this respect.
Prednimustine, a new antitumour drug, is a chlorambucil ester of prednisolone. The present prospective randomized study compares the effect of continuous low-dose (B) and intermittent high-dose (C) prednimustine in previously untreated patients with progressive CLL and WDLL. The control group received continuous chlorambucil/prednisolone therapy (A). One hundred and eighteen patients, 88 CLL and 30 WDLL, were evaluable. Response to therapy (greater than 50% improvement) was noted in 61, 55 and 57% in groups A, B and C respectively. The difference was not statistically significant. Time to response, response duration and survival did not show any differences between the groups. Responding patients survived longer than patients with stationary and progressive disease. Median survival time was 72 months from diagnosis and 52 months from start of therapy, with no differences between the treatment groups. Toxicity of prednimustine was usually mild and similar to that of the two constituents. Treatment schedule C showed a slight advantage with regard to frequency of side effects. In conclusion, in this study the therapeutic effect of prednimustine was equal to that of its constituents administrated separately.
Ethylene oxide, a gaseous sterilant extensively used within health care facilities, is known to be a mutagen in bacteria and in human lymphocytes. The Environmental Protection Agency as well as the National Institue of Occupational Safety and Health have recently stipulated certain conditions for the use of ethylene oxide despite the lack of case reports or epidemiologic studies concerning carcinogenicity. We report three cases of leukemia that occurred between 1972 and 1977 in a relatively small group of Swedish workers exposed to ethylene oxide. According to national statistics, 0.2 cases of leukemia would have been expected. The time-weighted average ethylene oxide concentration was 20+/-10 ppm.
Forty-four adult patients under 60 years of age with acute nonlymphoblastic leukemia were randomized for induction treatment with one of the following three regimens: R 1 = courses of daunorubicin on day 1 + ARA-C on days 1--5; R 2 = courses of daunorubicin on days 1 and 2 + ARA-C on days 4--8; R 3 = courses of daunorubicin-DNA complex on days 1--2 + ARA-C on days 4--8. Out of 14 patients, 9 went into remission on R 1, 6 out of 14 on R 2, and 8 out of 16 on R 3. The preliminary results suggest that daunorubicin-DNA complex has the same efficacy for inducing remission as daunorubicin alone, if the same time intervals and dosages are used.
In order to study the effect of oxymetholone therapy in advanced myelofibrosis, 11 patients (4 females, 7 males) were given, 3--5 mg per kg body weight, long-term oxymetholone treatment in a prospective multicenter study. Five cases had previously had a diagnosis of polycythemia vera. All patients had anemia initially, 4 leukocytopenia and 10 thrombocytopenia in addition. Hepato-splenomegaly was present in all cases but in varying degree. Five patients required regular blood transfusions before treatment. In 9 of the 15 courses given, there was normalization of the peripheral blood or substantial improvement (better than 3 g hemoglobin/dl or 50 X 10(9) platelets/1) after androgens. Significant effects were noted both on hemoglobin values and platelet counts. The need for blood transfusions ceased completely in all 5 cases. When oxymetholone treatment was reduced or interrupted 4 patients relapsed; 2 of them responded to a renewed course. The red cell counts returned to previous polycythemic values in one patient and another died from acute leukemia. The results of this study suggest that androgens might be of value in advanced cases of myelofibrosis with transfusion-requiring anemia or severe thrombocytopenia.
Total body haemoglobin was estimated by the alveolar equilibrium CO method and by dilution of 51Cr-tagged erythrocytes in 22 patients with a wide range of haemoglobin concentrations (51-190 g/l). The resulting regression equation: THBCO =47 + 0.81 X THbCr, where THn is expressed in grams, shows that with increasing THb successively lower values were obtained with the THbCO method as compared with the THbCr method. Individual values were calculated for the M-factor, i.e. the ratio of the haemoglobin affinities to O2 and CO. These values were positively and significantly correlated to the red-cell content of 2.3-diphosphoglycerate. The findings are consistent with a recent hypothesis that the effect of 2.3-DPG on CO affinity may not be equivalent to its effect on oxygen affinity. The discrepancy between the two methods of estimating THb may therefore be apparent only and due to a systematic variation in the M-factor.
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One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.
This is a prospective multi-center study in which patients with aregenerative anaemia were treated with a standardized high dosage regime of an anabolic steroid (oxymetholone, Anasteron). 53 patients were included and divided into two groups according to bone marrow cellularity. Furthermore the hypocellular group was subdivided in order to make comparison with earlier studies possible. In the hypocellular group, the frequency of remission was 56% and the 2-year-survival from the onset of symptoms was 75%. This is longer than in some earlier studies, perhaps because of possible differences in etiology and/or because of the effect of systematic high dosage, long term androgen therapy. Patient selection was minimized and was not considered to be of major importance. Patients with hypercellular marrows, on the other hand, responded poorly to androgens. In this group 63% died of acute leukaemia, which confirms earlier suggestions that this form of aregenerative anaemia, frequently is of a preleukaemic nature.
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77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.
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