[Why do we need therapy studies?].
Explore the source record for details and available documents.
Case-Control Studies↗
Biomedical subjects
S Sauter
Publications and source records attributed to S Sauter.
A review of physical exercises recommended for VDT operators.
This paper presents an evaluation of exercises that have been recommended for the prevention of musculoskeletal discomfort among VDT/office workers. 127 individual exercises were analysed for their suitability for performance in VDT workplaces. Additionally, each exercise was judged in terms of its safety and its compliance with principles of physiotherapy. Results showed that, in the majority of cases, the prepared instructions for the exercises were satisfactory and the exercises could be readily performed at the workstation. However, over a third of the exercises were conspicuous and potentially embarrassing to perform, and half would significantly disrupt the work routine. Additionally, a number of the exercises posed potential safety hazards, exacerbated biomechanical stresses common to VDT work, or were contraindicated for persons with certain health problems. These findings suggest a need for greater attention to both the practical and the therapeutic aspects of exercises promoted for VDT users.
Journal Article↗
Treatment trial with recombinant human erythropoietin in children with congenital hypoplastic anemia.
Explore the source record for details and available documents.
Adolescent↗
Acute onset deafness in a 4-year-old girl after a single infusion of cis-platinum.
Dose-dependent reduction of auditory function mainly in the high frequency range has been described as a common adverse side effect of cis-platinum. Here we report on a 4-year-old girl with osteosarcoma of the right distal femur who developed acute bilateral deafness 3 days after a single infusion of high-dose cis-platinum (150 mg/m2) during preoperative chemotherapy. Sudden disabling ototoxicity should be considered when administering high-dose cis-platinum to young children.
Acute Disease↗
Synergistic neurotoxicity of carbon tetrachloride/carbon disulfide (80/20 fumigants) and other pesticides in grain storage workers.
Neurophysiologic, neurobehavioral, and neuropsychologic profiles in 17 grain storage workers, 1 grain inspector, and 4 malting laboratory workers are described. The effects of CS2 toxicity as seen in viscose rayon workers as well as in experimental animals is remarkably similar to the clinical profile of our grain storage workers. CS2 use explains the dysfunction of peripheral axons, auditory nerve, the optic nerve, and the extrapyramidal system, as well as altered behavior and cognition changes. The signs and symptoms in these workers seem to be dose-related and we note that workers separated out from the areas where fumigation took place reported improvement not seen by fellow workers who continued the fumigant treatment routine. Likewise, malting laboratory workers exposed only to the grain dust from 3 to 7 years showed only minimal symptoms. Though a number of mechanism have been suggested for the alteration of neuropsychological function, the chelating ability of DDC derived from CS2 and its ability to markedly increase copper and zinc within the central nervous system suggests a mechanism of toxicity analogous to copper intoxication as in Wilson's Disease and may explain the production of extrapyramidal symptoms in these patients. Chelation of copper might prove therapeutic in CS2 poisoning. It is obvious that both basic and clinical research will be necessary to sort out the questions raised. We applaud the EPA's decision to ban the use of 80/20 fumigants and also methyl bromide, and trust that similar toxic substances be carefully studied before their selection for replacing these previous toxic agents. We further decry the technique of re-introducing grain dust into the food chain rather than destroying it, since the dust contains very high residues of fumigant material. We speculate on the possible role of CS2 and other pesticides in the food chain and the incidence of Parkinsonian symptoms in these patients and the general public.
Adult↗
Deposition of beta 1H globulin in kidneys of patients with immune renal disease.
Renal biopsies from patients with a variety of immune type renal diseases were examined by immunofluorescence for the presence of C3 and its control protein, beta 1H globulin. Deposits of beta 1H were found in every instance (21 of 21 biopsies) in which C3 deposits were observed, irrespective of the underlying disease resulting in the C3 deposits, including lupus nephritis, acute poststreptococcal glomerulonephritis, idiopathic membranous glomerulonephritis, and Goodpasture's syndrome. In no instance was beta 1H found independently of C3. As previously shown in in vitro systems, beta 1H also binds to C3, presumably C3b, during activation of the complement system in immunologically induced renal disease.
Anti-Glomerular Basement Membrane Disease↗
Stimulation of ornithine decarboxylase activity and inhibition of S-adenosyl-L-methionine decarboxylase activity in leukaemic mice by methylglyoxal bis(guanylhydrazone).
Administration of methylglyoxal bis(guanylhydrazone) to leukaemic mice results in an early depression followed by a marked elevation of S-adenosyl-l-methionine decarboxylase activity. Further, there is an early prolonged increase in the activity of ornithine decarboxylase, the initial enzyme in the polyamine biosynthetic pathway. Because of the profound effects of methylglyoxal bis(guanylhydrazone) in vivo on the polyamine biosynthetic pathway, the drug can no longer be considered a specific inhibitor of spermidine synthesis.
Adenosine↗
Effects of the serotonin antagonist amesergide on reproduction in female rats.
Amesergide, a serotonin (5-HT2) antagonist intended to treat depression, was administered orally to female CD rats (20/group) at doses of 0, 3, 10, or 30 mg/kg to evaluate effects on mating, fertility, litter size, live birth index (100 x total liveborn progeny/litter size), progeny survival, and weight gain of each litter. The treatment period extended from two weeks prior to mating through postpartum day 21 to cover possible effects of estrous cycle, mating, gestation, and postpartum events. Twenty additional female rats were given 30 mg/kg through gestation day 18, after which they received the acacia vehicle (recovery group). All females were allowed to deliver naturally and rear their progeny. On postpartum day 8, progeny in the control, 30 mg/kg and 30 mg/kg recovery groups were removed from dams for 4 h. Progeny were weighed as litters, returned to the dams for a 1-h nursing period, and then weighed again to provide an indication of milk intake. Mating and fertility, using the present study design, were not affected by treatment with amesergide. No effects were observed on litter size, live birth index, or progeny survival. In contrast, treatment with amesergide throughout gestation and lactation produced a significant dose-related depression in progeny body weight gains. However, when treatment was discontinued after day 18 of gestation (30 mg/kg recovery group), progeny body weight gains did not differ from those of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Changes in blood coagulation in treatment with ALL-BFM-90 and NHL-BFM-90 protocols].
1. Treatment according to the ALL/NHL-BFM 90 protocol I (induction phase) caused multiple and severe coagulation changes in all 14 patients of our study. Glucocorticoids alone made Fibrinogen drop to 148 mg/dl, AT III and Protein C rise to 136% or even 179% respectively. After day 12, immediately following the start of therapy with Coli-Asparaginase (ASP), fibrinogen continued to drop to reach its lowest average value of 46 mg/dl on day 24. Anticoagulant factors like plasminogen (lowest average value: 36%), AT III (47%) and Protein C (93%) dropped abruptly. These alterations were reversed after discontinuation of Glucocorticoids and ASP. During consolidation (protocol II) similar alterations are observed as in protocol I when Glucocorticoids are applied alone. However, after Erwinia-ASP there is no fall in AT III, plasminogen, and Protein C as is observed in protocol I with Coli-ASP. 2. Severe hemorrhages or thromboses are uncommon as compared to the degree of coagulation changes which can be regularly observed. Complications occur more often in girls. Most of them are seen during the 2nd or 3rd week of simultaneous ASP-Glucocorticoid therapy. 3. To avoid twofold alteration of hemostasis it should be considered to apply Glucocorticoids and ASP separately and to replace Coli-ASP by Erwinia-ASP. The efficacy of prophylactic replacement of decreased coagulation factors has not yet been confirmed. Immunologic and infectious side effects have to be taken into consideration. 4. More definite recommendations can be given when each suspected bleeding and/or thrombosis is confirmed by imaging procedures, when it is documented and registered, and when coagulation studies are performed during the critical phase.
Antineoplastic Combined Chemotherapy Protocols↗
[Incidence, clinical markers and prognostic significance of immunologic subtypes of acute lymphoblastic leukemia (ALL) in children: experiences of the ALL-BFM 83 and 86 studies].
In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T-ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre-pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age.
Antigens, CD↗
Effect of glucocorticoids, E. coli- and Erwinia L-asparaginase on hemostatic proteins in children with acute lymphoblastic leukemia.
BACKGROUND: The concentrations of plasma hemostatic proteins were analyzed prospectively in 42 children with acute lymphoblastic leukemia (ALL), treated according to the protocol ALL-BFM-90. PROCEDURE: Treatment included glucocorticosteroids (GC), E. coli L-asparaginase (Asparaginase, Medac) or Erwinia L-asparaginase (Erwinase, Speywood), vincristine, anthracyclines and intrathecal methotrexate. The analysis of hemostatic proteins was performed during induction and re-induction therapy. RESULTS: At diagnosis, the plasma concentrations of fibrinogen, antithrombin III (AT), plasminogen and protein C were within normal limits, whereas the von Willebrand factor antigen (vWF:Ag) was elevated. After eight days of mono-therapy with GC the concentration of fibrinogen decreased to 59%, vWF:Ag decreased to 67%, AT increased to 124%, protein C increased to 201% of the initial value (mean all p < or = 0.01), while the concentration of plasminogen remained unchanged. During the re-induction phase, the concentrations of the hemostatic proteins, with exception of vWF:Ag, altered in a similar way in response to GC as observed during the induction phase. Administration of two doses of E. coli L-asparaginase (10,000 U/m2) during the induction therapy led to a significant decrease of AT (123 +/- 24 to 63 +/- 15%/mL), protein C (168 +/- 34 to 87 +/- 19%/mL), plasminogen (94 +/- 21 to 41 +/- 12%/mL) and fibrinogen (148 +/- 59 to 79 +/- 30 mg/dL, p < or = 0.01 for all parameters). In contrast, administration of two doses of Erwinia L-asparaginase (10,000 U/m2) during re-induction therapy did not lead to change in the concentration of AT, protein C or plasminogen, and the decrease in fibrinogen (162 +/- 17 to 121 +/- 24 mg/dL) was less pronounced. CONCLUSIONS: Our results indicate that GC and E. coli L-asparaginase, in particular, induce hemostatic alterations which have implications on our understanding of thrombotic and hemorrhagic events during the treatment of ALL in children.
Adolescent↗
[Bacteremic episodes in pediatric oncologic patients, especially caused by the Streptococcus viridans group].
BACKGROUND: The management of infectious complications plays a major role in the care for pediatric cancer patients. The majority of infections in the neutropenic patient present as fever of unknown origin without recovering a pathogen from the blood stream. The careful evaluation of bacteremic episodes is essential, since knowledge of the bacterial spectrum expected is crucial for the successful anti-infective treatment. PATIENTS AND METHODS: From 1985 to 1995 all bacteremic episodes in pediatric oncology patients at the University Children's Hospital Freiburg were retrospectively analyzed with respect to the pathogens encountered, the antibiotic susceptibility profile and the underlying conditions. RESULTS: Overall, 113 bacteremic episodes were encountered in pediatric oncology patients, 68 of them in patients with hematological malignancies, and 45 in patients with solid tumors. In both patient groups, gram-positive bacteria were predominant with 72% and 58%, respectively. In patients with hematological malignancies, viridans streptococci were the most frequently isolated pathogens (35%) with a relevant morbidity (29% of patients developed a severe sepsis syndrome and/or ARDS), but were found only in 9% of patients with solid tumors. In 28% of patients with leukemia or lymphoma, gram-negative rods were cultured, in 6% Pseudomonas spec., in 4% Acinetobacter spec., and in 18% enterobacteria. In patients with solid tumors, in 38% gram-negative rods were isolated, 7% Pseudomonas spec., 16% Acinetobacter spec., 16% enterobacteria. In 3 patients, fungemia was observed. The antibiotic susceptibility profile was quite favorable in both, gram-positive and -negative bacteria: none of the gram-positive isolates was resistant to vancomycin, none of the Staphylococcus aureus isolates was resistant to oxacillin. All gram-negative bacteria were fully susceptible to ceftazidime, imipenem and ciprofloxacin. CONCLUSION: Gram-positive bacteria account for 2/3 of all bacteremic episodes in pediatric oncology patients. Streptococcus viridans was the most important pathogen in hematological malignancies accounting for a significant, pathogen-specific morbidity.
Adolescent↗
[Kinetics of myelopoietic regeneration and mobilization of CD34-positive cells within the scope of the NB90 Neuroblastoma Therapy Study].
Hematological and clinical data of 14 children with neuroblastoma treated according to the German neuroblastoma therapy study NB 90 were analyzed. Therapy included 4 or 8 intensive therapy elements N1 (Etoposide 125 mg/m2 day 1-4, Vindesine 3 mg/m2 day 1, Cisplatin 40 mg/m2 day 1-4) and N2 (Vincristine 1.5 mg/m2 day 1 + 8, Dacarbazine 200 mg/m2 day 1-5, Ifosfamide 1500 mg/ m2 day 1-5, Doxorubicin 30 mg/m2 day 6 + 7) in alternating order. The hematological recovery was studied after 86 therapy elements N1/N2. G-CSF had been given in 23 therapy courses, while no cytokine was administered in 63 therapy courses. Mobilization of CD34+ cells was studied in 13 therapy courses with G-CSF. Severe myelosuppression with an absolute neutrophil count < 500/microL was noted 2-4 weeks after each therapy element. The use of G-CSF did not prevent, but shortened neutropenia. There was no difference in the number of infections nor time delay of therapy between the courses with or without G-CSF. In 11 therapy courses G-CSF was started on the day following the last chemotherapy dose (N1: day 5; N2: day 9). In 12 therapy courses G-CSF was given delayed, starting day 12 after the initiation of therapy. Kinetics of granulocyte recovery was similar in the early or delayed application of G-CSF. Neutrophil recovery after the therapy element N1 was earlier and faster compared to that of therapy element N2. The more rapid rise of the neutrophils after the N1 element was accompanied by an effective mobilization of CD34+ cells. Taking into account the limitations of this retrospective study, the data may help to optimize the application of G-CSF in a very intensive therapy study like NB90.
Adolescent↗
[Oncologic after-care--a patient-oriented concept. Basic diagnostic plan for pediatric oncology patients].
With intensive treatment many children and young adults with cancer can be cured of their disease. Therefore, the recognition of late effects of therapy will become increasingly important. Future concepts of follow-up care in pediatric oncology will have to serve two purposes: First, to determine the status of the malignant disease with early diagnosis of relapse and second, to recognize relevant side effects of treatment. We present a comprehensive approach of follow-up care which is primarily based on the definition of risk criteria for the development of relevant organ toxicity after different treatment modalities. For each patient a standardized summary of therapy delivered is documented. According to the definition of the risk criteria an individualized schedule for follow-up is decided upon. We hope that this structured concept will result in appropriate patient care while keeping the diagnostic efforts and costs limited.
Adolescent↗
[Severe neuropathy after chemo- and radiotherapy of Ewing sarcoma].
A 15 year old patient presenting with a lumbar Ewing's Sarcoma was treated according to the EICESS-92 pilot study (EVAIA branch). Local therapy consisted of definitive irradiation given simultaneously to chemotherapy courses 5 to 7. Close to the end of treatment the patient developed progressive peripheral neurologic deficits. Such combined toxic treatment side effects are unique and unforeseen in the study protocol.
Adolescent↗
[Concept and interim result of the ALL-BFM 90 therapy study in treatment of acute lymphoblastic leukemia in children and adolescents: the significance of initial therapy response in blood and bone marrow].
In the ongoing trial ALL-BFM 90 for the treatment of childhood non-B cell acute lymphoblastic leukemia (ALL) 1468 unselected patients (pts) were enrolled from 84 centers in Germany and Switzerland from 4/90 to 12/93. Based on the results of the previous trial ALL/NHL-BFM 86 this treatment program focused especially on therapy modifications for average (MRG) and high risk (HRG) pts, on the evaluation of therapy response for prognosis, and on the identification of high risk pts by molecular genetics. For average risk pts consolidation therapy was intensified by the addition of L-asparaginase (L-ASP) on a randomized basis. In HRG induction and consolidation therapy was modified by introduction of early intensification elements that had proved to be effective in relapsed pts. This patient group was randomized for the evaluation of the effects of G-CSF administered in the intervals between the intensification elements. Distribution of the 1376 eligible pts into the three treatment arms SRG (standard risk), MRG, and HRG was as expected (17 pts not yet assigned): 385 pts (28.0%), 834 pts (60.6%), and 140 pts (10.2%), respectively. Treatment consisted of the 8-drug induction (Protocol I), consolidation (Protocol M), reinduction (Protocol II), and maintenance therapy (total therapy duration 24 months). The drug doses and combinations were only slightly modified compared to the previous study ALL-BFM 86 with the exception of the randomized L-ASP containing arm MRG-2 (Protocol M-A) and group HRG. Preventive cranial irradiation was reduced to 12 Gy and applied to MRG and HRG pts only. As in study ALL-BFM 86, the initial response to a 7-day exposure to prednisone and to the first intrathecal injection of MTX at diagnosis was evaluated at day 8 of treatment with regard to blast count in peripheral blood (PB). In addition, pts were now investigated for the presence of blasts in the bone marrow (BM) at day 15 of treatment to compare the prognostic power of both response parameters. Identification of translocation t(9; 22) and/or BCR-ABL rearrangement characterized a small subgroup of pts that were not detected by poor initial therapy response. These pts were enrolled in HRG for more intensive treatment including allogeneic bone marrow transplantation (BMT). After a median observation time of 22 months, the overall probability for event-free survival (p-EFS) is 82 +/- 2%. 11 pts (0.8%) died before complete remission (CR) was achieved, 15 pts (1.1%) died while in CR for reasons other than relapse.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphomas in children and adolescents. Part 2: An intermediate term analysis of the non-B-NHL therapy group. BFM Study group].
The goals of study NHL-BFM 90 for the therapy group Non-B NHL are to prospectively evaluate the dynamic of tumor regression and the persistence of a residual mass after induction therapy for its prognostic impact. Patients (pts) of stages I and II receive induction composed of prednisone, vincristine (VCR), daunorubicin, L-asparaginase (L-ASP), cyclophosphamide (CP), cytarabine (ARA-C), 6-mercaptopurine (6-MP) and intrathecally (i.th.) methotrexate (MTX), followed by consolidation (6-MP,MTX 5 g/m2 x 4, MTX i.th.), and maintenance up to 24 months. Pts of stages III and IV receive additionally reinduction (Dexamethasone, VCR, doxorubicin, L-ASP, CP, ARA-C, 6-thioguanine, MTX i.th.) and cranial irradiation. Pts with < 70% tumor regression at day 33 of induction receive an intensified chemotherapy. Pts with > 70% tumor regression at day 33 but a persistent mass at the end of induction have a surgical resection. Pts with a completely necrotic residual mass continue with consolidation therapy. Pts with active residual lymphoma receive an intensified chemotherapy. No local radiotherapy is given. From 4/1990 to 12/1992, 80 pts were registered; 71 pts are evaluable for response. The distribution of stages is as follows: 6, 1, 47, 17 pts of stage I, II, III, IV, respectively. The probability of event free survival at 3 years is 87 +/- 4% for the whole group (median observation time 21 months). 66 pts are evaluable for the dynamic of response.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[NHL-BFM 90 therapy study in treatment of malignant non-Hodgkin's lymphoma in children and adolescents. Part 3: An intermediate term analysis of the B-NHL/B-ALL].
The aims of trial NHL-BFM 90 for patients (pts) suffering from B-cell neoplasms are to prove whether: 1. Treatment for pts with complete resection can be reduced from 3 to 2 therapy courses; 2. Results for pts of stage III with large abdominal tumors can be improved by high dose (HD) chemotherapy; 3. Survival for pts with incomplete initial response can be improved by therapy intensification; 4. Intraventricularly applied CNS chemotherapy can improve the outcome for CNS positive pts. Therapy is stratified into 3 branches. Branch 1: completely resected; branch 2: not resected, extra-abdominal localization only or abdominal localization and LDH < 500 U/l; branch 3: abdominal localization and LDH > or = 500 U/l, and all pts with BM or/and CNS involvement or multifocal bone disease. A 5-day prephase is followed by 2 (R1), 4 (R2), 6 (R3) therapy courses composed of dexamethasone (DEXA), methotrexate (MTX) 5 g/m2/24 h (in branch R1, 500 mg/m2), MTX/Cytarabine (ARA-C)/prednisolone (PRED) i.th., vincristine (not in branch R1), ifosfamide alternating with cyclophosphamide, ARA-C/etoposide (VP16) alternating with doxorubicin. CNS pos. pts receive MTX/ARA-C/PRED applied intraventricularly. Pts with incomplete response after 2 courses receive an intensification (DEXA, Vindesine, HD-ARA-C, VP16, and MTX/ARA-C/PRED i.th.). Pts with viable tumor after the intensified course receive mega-dose chemotherapy with autologous BM rescue (aBMT). From 4/1990 to 12/1992, 228 pts were registered; 212 pts are evaluable for response. The probability of event free survival (pEFS) at 3 years is 89 +/- 2% for the whole group, 97 +/- 3% for pts of branch R1 (n = 32), 99 +/- 1% for patients of branch R2 (n = 87), and 77 +/- 4% for patients of branch R3 (n = 94) (median observation time 21 months). 7 pts of branch R3 died early due to infections. 15 pts failed therapy (one pt each in branch R1, and R2, 13 pts in branch R3). pEFS for pts with stage III abdominal disease and LDH > or = 500 U/l is 80 +/- 6 as compared to 53 +/- 8% in the preceding studies (p < .02). Of 13 evaluable pts with CNS disease 3 died early of infection, however none suffered from relapse. Only 1 of 22 pts of branch R2 who had residual tumors after 2 therapy courses suffered from progress in contrast to 9 of 33 such pts of branch R3. Only 2 pts had viable tumor after the intensification course CC. They received aBMT, both are in CCR.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗