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Biomedical subjects

H Pralle

Publications and source records attributed to H Pralle.

At least 73 records · Page 4Linked to original sources

Staging systems for multiple myeloma: a comparison.

In 152 patients with multiple myeloma who had been treated with cytostatic agents the prognostic value of seven staging systems was evaluated: Carbone et al (1967); Acute Leukemia Group B (ALGB) and Eastern Cooperative Oncology Group (ECOG) (Costa et al, 1973); Southeastern Cancer Study Group (SECSG) (1975); Durie & Salmon (1975); Alexanian et al (1975); Merlini et al (1980); British Medical Research Council (1980). The staging systems of the ALGB (Costa et al, 1973) and SECSG (1975), both dividing patients into 'good risk' and 'poor risk' groups, showed significantly different survival curves. Nevertheless, despite statistical significance the observed differences were rather small. In the systems of Carbone et al (1967), Merlini et al (1980), Alexanian et al (1975) and Durie & Salmon (1975) some of the differences in the survival curves were statistically significant while others were not. Our data best fitted into the British Medical Research Council (1980) staging system, the survival curves of all three stages showing significant differences, with median survival time dropping from 83 months in stage A to 52 months in stage B and 26 months in stage C. Nevertheless, none of those systems was clearly superior to single risk factors, especially creatinine and haemoglobin.

Adult↗

A new red blood cell cold autoantibody (anti-Me)

A new red blood cell (RBC) cold autoantibody (anti-Me) is presented which was detected in a patient with autoimmune hemolytic anemia of 'cold type' associated with Waldenström's macroglobulinemia. The autoantibody was of the IgM (Kappa) class, had a moderate titer, and reacted with cord as well as with adult RBC. Its hemagglutinating activity against RBC was markedly increased in the presence of preheated human milk, but not in the presence of simple sugars or preheated casein. The data suggest that the antibody is directed against a new (glycolipid) antigen common to human RBC termed Me antigen ('milk enhanced').

Anemia, Hemolytic, Autoimmune↗

Therapy of priapism in high counting myeloid leukemia--a combined oncological-urological approach. Two case reports.

Two cases of leukemic priapism are described. Both patients underwent a combined oncological (antileukemic chemotherapy, cell depletion by leukapheresis) and urological (transglandular cavernosum-spongiosum shunt, heparin lavage of the corpora cavernosa) therapy. Cytologically necrobiotic tumor cells could be identified in the corpus cavernosum aspirates causing blood stasis in the corpora cavernosa initiating priapism. Only sufficient venous outflow by additional transglandular cavernosum-spongiosum shunt completed therapy, effected a rapid detumescence and led to subsequent ability of erection and coitus. This suggests the necessity of additive surgical treatment in every patient suffering from leukemia and priapism, if spontaneous detumescence under chemotherapy is not obvious.

Adolescent↗

A sensitive method for immunophenotyping stored leukemia and lymphoma cells with preservation of morphological detail.

We describe a method by which density-separated mononuclear preparations of blood and bone marrow may be stored and batch-processed for immunophenotyping by the indirect immunoperoxidase (IP) technique. The method gives excellent preservation of cellular detail thus permitting clear morphological categorization of IP-positive and IP-negative cells. We compared the immunofluorescence (IF) and IP techniques for estimation of the proportions of cells displaying a variety of antigens; with normal blood cells the results were closely similar but with chronic lymphocytic leukemia (CLL) cells, IP was superior to conventional IF. Using 910 D7, a new anti-la antibody, we were able to observe directly the presence of la-positive lymphocytes and monocytes in normal peripheral blood and la-positive granulocyte precursor cells from 2 cases of chronic granulocytic leukemia (CGL) in transformation. The method is useful for immunophenotyping of cases of lymphoproliferative disorder (LPD) and for morphological identification of specific antigen-positive cells.

Antibodies, Monoclonal↗

[Results of therapy with high-dose cytosine arabinoside].

Four patients with acute leukemias resistant to various ARA-C containing regimens and one patient with rapidly progressive malignant nonseminomatous tumor of the testis, who failed to conventional therapy were treated with HD ARA-C from december 1979 to september 1980. The drug was monitored by HPLC in plasma and in CSF. The first patient received only one course of HD ARA-C, developed fever and died of septicemia ten days later. The leucocyte count of her AML (FAB 2) decreased from 120,000/microliter to 30,000/microliter on the third day after HD ARA-C. Patient 2 reached CR criteria of the bone marrow for 23 days, then resistant AML (FAB 2) recurred. A male patient of 30 years was treated for recurrent acute undifferentiated leukemia (AUL) with a high cumulative dose of 176 gs of ARA-C. The repeated courses of treatment included a period of 50 days of CR. Toxicity was remarkable including pulmonal and cerebral dysfunction. A fourth patient with monocytic leukemia did not respond to HD ARA-C, neither did the patient with the malignant teratoma. Adverse reactions were tolerable. Only the third patient suffered from severe toxicity, pneumonitis, blurring vision, cerebral dysfunction and dermatitis. His pretreatment regimen had included X-ray prophylaxis to the skull. Since there was no possibility to prolong the remission duration in 1980, we decided not to treat further patients with HD ARA-C. Nowadays bone marrow transplantation offers some patients a capability of eradication of the leukemic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Antigens and circulating immune complexes related to the primate retroviral glycoprotein SiSVgp70. Indicators of early mortality in human acute leukemias and chronic myelogenous leukemias in blast crisis.

Human sera contain antigens and also circulating immune complexes that are related to the primate retroviral envelope glycoprotein gp70 of simian sarcoma/simian sarcoma associated virus (SiSV) and of gibbon ape leukemia virus (GaLV). SiSVgp70 related antigens (AG) and immune complexes (IC) are detected both in leukemic and in nonleukemic sera. In a further analysis of these data, the prognostic significance of SiSVgp70 related AG and IC in leukemic patients was examined. The data show that the presence of SiSVgp70 related AG and IC indicates an unfavorable clinical course and a shorter survival time in acute leukemias (AL) and in chronic myelogenous leukemia in blast crisis (CML-BC). Survival data of 56 of 64 patients tested were analyzed (38 patients with AL and 18 patients with CML-BC). Patients with AL whose sera were positive for SiSVgp70 related AG and IC had a median survival time of 9.5 months after diagnosis versus 16 months for patients negative for such AG and IC. This difference in survival time was more pronounced for patients with acute nonlymphocytic leukemia (ANLL) (6.5 versus 19 months). The difference in survival between SiSVgp70 related AG- and IC-negative and positive groups as tested by life table analysis (log-rank test) is significant (P less than 0.05). Patients with AL of the AG- and/or IC-positive group had fewer complete remissions. Patients who had no remissions belong to the AG- and/or IC-positive group (P = 0.06). Patients with CML-BC whose sera were positive for SiSVgp70 related AG and/or IC had a median survival time of 2 months after diagnosis versus 7 months for patients with sera negative for such AG and IC. As tested by log-rank test, survival curves between the two groups are significantly different (P less than 0.05). These findings suggest that SiSVgp70 related AG and IC may play an important role in the course of acute leukemia and can provide useful prognostic information.

Acute Disease↗

Determination of phosphoethanolamine in urine or in the presence of high taurine concentrations.

Phosphoethanolamine forms a low-solubility lead salt, which may be precipitated from urine together with inorganic phosphate, thus separating taurine, urea, and other interfering substances of chromatographic determination. Fluorometric detection of phosphoethanolamine with o-phthaldialdehyde after elution from a Dowex 50-X10 column enhances the specificity of the method once more. The method described is fast and easy to perform.

Chemical Precipitation↗

Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family.

Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient. Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase. The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered. The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogeneous disorder which includes both severe and clinically mild forms.

Adult↗

Ex vivo antigen preparation for the serological detection of drug-dependent antibodies in immune haemolytic anaemias.

Two patients with severe, intravascular haemolysis due to drug-dependent antibodies are described. The antibodies were directed against presumptive metabolites of buthiazide (International Non-proprietary Name, butizide) and nomifensine. Their detection was possible only in the presence of ex vivo antigens (i.e. fresh serum of volunteers after ingestion of the drugs) while in vitro antigen preparations yielded inconclusive results. Both antibodies lysed normal red cells in the presence of ex vivo antigens and complement. The buthiazide-related antibody was IgG (subclass IgG1), the nomifensine-related antibody was IgM. We conclude that the use of ex vivo antigens is of great importance in the serological evaluation of cases with suspected drug-dependent immune haemolysis.

Anemia, Hemolytic↗

Glucocorticoid receptor level, terminal deoxynucleotidyl transferase activity and initial responsiveness to prednisone and vincristine in leukemia.

We have investigated glucocorticoid receptor (GR) level, terminal deoxynucleotidyl transferase (TdT) activity and the initial responsiveness to prednisone and vincristine in 31 patients with acute lymphatic leukemia (ALL) and with chronic myelogenous leukemia in blast transformation (CML/BT). All 11 patients with low levels of GR (5,000 binding sites per cell) were resistant to this initial treatment whereas 13 of the 20 patients with high levels of GR responded readily. The correlations between clinical responsiveness and TdT activity were significant to the p less than 0.005 level but there was no linear correlation (r = 0.3427) between GR-level and TdT activity. High levels of both GR and TdT seemed to be associated with better prognosis in patients with these leukemias. Thus the determination of GR and TdT might help selection of patients likely to respond to prednisone and vincristine in ALL and CML/BT.

Adolescent↗

[Phase II study of AMSA in adults with acute therapy-refractory leukemias].

The acridine derivative AMSA, Amsacrine, is a new anticancer drug which was effective in patients with advanced AML and ALL in studies performed in USA. In a multicenter phase II trial we treated 27 patients with acute resistant leukemia with AMSA. All presented progressive disease following several drug combination regimens. Out of the 25 evaluable patients 5 were resistant to primary therapies, 13 were in 2nd relapse, 6 in 3rd, and 1 in 4th relapse. Dosage was 75 mg/m2, iv, day 1-7, all 3-5 weeks. On an average, only 76% of the planned dose per cycle could be given, due to severe leucopenia. From 21 patients with ALL, 1 CR and 3 PR were observed; the 3 patients with ALL presented 1 CR and 1 PR. 1 AUL showed progressive disease. In all patients a marked cell reduction could be observed in the peripheral blood. The general tolerance was good. The most important side-effect was bone-marrow toxicity, 48% (12/25) presented leucopenia less than or equal to 600/mm3, 5 (20%) had fatal septic complications. All 5 early death presented high initial leucocyte counts of greater than or equal to 32.000 mm3 as a common risk factor. In conclusion, AMSA is an effective drug in heavily pretreated patients with AML and ALL.

Adolescent↗

[Therapeutic response of various histological osteosarcoma subtypes to high-dose methotrexate treatment].

The successful or unsuccessful chemotherapy of osteosarcoma has given rise to the division of these tumors into responders and non responders from the clinical point of view. In order to work out drug sensitive tumor components we studied 9 osteosarcomas by a histological subdivision of the osteosarcoma tissue into 6 subtypes. Seven of the 9 osteosarcoma patients had developed lung metastases under adjuvant high dosage methotrexate (HDMTX) therapy. The aim was to identify the components of the primary tumors which had endured HDMTX-therapy as lung metastases. As HDMTX-sensitive histologic differentiation form of osteosarcoma tissue we regarded the no matrix producing-subtype (III), because it did not occur in the lung metastases. The classical subtype (IV) seems to be only partially sensitive because the corresponding lung metastases showed a higher osteoblastic differentiation with increased osteoid production. No therapeutic effect could be observed in the chondromatous (I) and in the sarcomatous (II) subtypes as well as in the two subtypes with intensive osteoid production being termed trabecularly sclerosing (V) and massively osteoid producing subtypes (VI).

Adolescent↗

Clinical results and pharmacokinetics of high-dose cytosine arabinoside (HD ARA-C).

Four patients with acute nonlymphoblastic leukemia and one malignant teratoma refractory to conventional chemotherapy were treated with high doses of cytosine arabinoside (HD ARA-C). They received up to 12 cycles of 1.8 to 3 g/m2 every 12 hours applied by 2-hour infusions. A total of 55 HD ARA-C infusions was performed. All leukemic patients responded. A complete clearance of blasts from the bone marrow was observed in two patients following 8-12 cycles of 3 g/m2. However, relapses occurred after three and seven weeks, in one case with resistance to HD ARA-C. The patient with malignant teratoma did not respond. No severe toxicity emerged even after repeated applications. Adverse reactions included moderate nausea and vomiting (4 patients), diarrhea (2 patients), hepatic dysfunction (1 patient), bone pain (1 patient), blurred vision (1 patient), conjunctivitis (1 patient), and exanthema with partial epidermiolysis (1 patient). Granulocytopenia occurring between 3-8 days after having started the therapy, subsided within 4-25 days. Plasma levels of ARA-C and the metabolite uracil arabinoside (ARA-U) were monitored. At steady state plasma concentrations of ARA-C were 32-97 microM (8-24 micrograms/ml). ARA-C disappeared from the plasma mono- or biphasic with a terminal half-life (t50%) of 7.8-12.6 minutes. The total clearance (Cl) of ARA-C varied between 1.7 and 2.9 liters/kg . h, and the distribution volume (Vss) between 0.44 and 0.86 liters/kg. Cerebrospinal fluid (CSF) levels of ARA-C reached 10-15% of steady state concentrations in plasma.

Adult↗

Prognostic factors in COPP-treated patients with Hodgkin's disease.

In a recently published review of the literature [40] we came to the conclusion that the Ann-Arbor staging classification is of limited prognostic value for chemotherapy of Hodgkin's disease (Table 2). Four risk factors accounted for impaired complete remission rates: stage IVB, lymphocyte depletion or not classifiable histologic type, previous chemotherapy, and older age. Fifty-eight evaluable patients were treated with COPP; 23 reached a complete remission (40%). Disease-free survival was 31%, overall survival 49% after five years [33]. Besides the known risk factors, impaired bone marrow function (leucocyte counts less than 4 X 10(9)/l, platelet counts less than 100 X 10(9)/l) at the start of therapy was associated with poor treatment results: none of six patients achieved a complete remission [41]. Eleven of 16 patients with no and 11 of 23 patients with one risk factor achieved a complete remission, as did only one patient with more than one risk factor. Survival rates after 30 months were: 87% with no, 66% with one, 36% with two, and 13% with more than two risk factors. We can conclude from our results that the prognosis of patients undergoing chemotherapy for Hodgkin's disease depends on the number of risk factors.

Cyclophosphamide↗

Multicentre study on intensified remission induction therapy for acute myeloid leukemia.

In a cooperative study at 13 centres in the Federal Republic of Germany, 213 adult patients with AML were treated for remission induction by a 9-day regimen consisting of cytosine arabinoside, daunorubicin and thioguanine (TAD) according to previously described sequencing. Complete remission was achieved in 70% of all patients. Complete remission rate was 57% in the 49 patients 60 years of age and older and 74% in the 164 patients under 60 years. Sixty-eight per cent of all complete remissions and 75% of those in the higher age group were induced by one induction course. Median survival was 10 months for all patients treated and 16 months for responders. Median remission duration was 13 months with 72 patients still in continuous remission for 1-31 months. Remission duration was not significantly different for patients treated either by monthly maintenance therapy or induction type consolidation without further therapy. However, patients completing two consolidation courses had a significantly longer remission duration of 22 months. Compared to similar multicentre studies on AML therapy the intensified induction regimen applied in this study shows an improvement even in older patients.

Adolescent↗