[Patient-physician communication. Physicians must be trained to tell bad news].
Explore the source record for details and available documents.
Communication↗
Biomedical subjects
S Sauter
Publications and source records attributed to S Sauter.
Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens.
Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection.
Animals↗
Central venous catheter infection by Aspergillus fumigatus in a patient with B-type non-Hodgkin lymphoma.
Invasive Aspergillus infection is still a major problem in immunocompromised patients. A central venous catheter infection by Aspergillus fumigatus, however, has not yet been reported. We describe the case of a 10-year-old female patient with B-type non-Hodgkin lymphoma treated according to the German chemotherapy protocol NHL-BFM 90. Isolation of Aspergillus fumigatus from the blood was the first hint of invasive aspergillosis. A central venous catheter-associated infection was suggested, since Aspergillus was also isolated from the thrombotic tip of the removed catheter. Secondary pulmonary aspergillosis was documented radiologically. The patient was treated successfully by Ampho-thericin B and Itraconazol and explantation of the central venous catheter under conditions of complete hematopoietic regeneration of the bone marrow with omission of the final chemotherapeutic cycle.
Antineoplastic Combined Chemotherapy Protocols↗
Pleuro-pulmonary blastoma: a case report and review of the literature.
Pleuro-pulmonary blastoma is a rare malignant lung tumor in children and distinct from ordinary pulmonary blastoma of adulthood. Combination chemotherapy plays an important role in the treatment of this tumor, but so far no attempt of high dose chemotherapy with subsequent bone marrow or blood stem cell transplantation has been published. The case is reported of a 2-year-old boy with pleuro-pulmonary blastoma who achieved partial remission with conventional chemotherapy and surgery. Subsequent administration of high dose melphalan, etoposide, and carboplatin, followed by autologous blood stem cell transplantation resulted in a 3-month disease-free interval but did not prevent eventual local recurrence, leading to death within a few weeks. Clinical presentation, pathology, management, and prognosis are discussed and the literature reviewed.
Child, Preschool↗
Hemophagocytosis: a complication of acute Q fever in a child.
We describe an 11-year-old boy with acute Q fever complicated by hemophagocytosis. In addition to pancytopenia, the boy presented with hyponatremia, hypofibrinogenemia, and changes in lipid metabolism. Examination of a bone marrow aspirate revealed striking hemophagocytosis. All of the pathological changes were caused by an activated macrophage system. We also discuss the possible role that pathogenetic mechanisms play in these changes.
Acute Disease↗
Non-Hodgkin's lymphomas of childhood and adolescence: results of a treatment stratified for biologic subtypes and stage--a report of the Berlin-Frankfurt-Münster Group.
PURPOSE: To prove the efficacy of a treatment stratified according to histology for children with non-Hodgkin's lymphoma (NHL), including acute B-cell leukemia (B-ALL). PATIENTS AND METHODS: From October 1986 to March 1990, 302 assessable patients, 0.6 to 17.8 years of age, with newly diagnosed NHL were enrolled onto study ALL/NHL-BFM 86. Fifty percent of patients had Burkitt-type lymphomas, including B-ALL; 24% had lymphoblastic lymphoma; 18% had diffuse large-cell lymphoma; and 8% had an NHL not further classified. Therapy group B included Burkitt's-type lymphomas, B-ALL, and most large-cell lymphomas including Ki-1 anaplastic large-cell lymphoma. Patients with stage I and II disease resected received three, while all others received six, 5-day therapy courses (dexamethasone, methotrexate [MTX] 0.5 g/m2 [5 g/m2 for stage IV and B-ALL], and intrathecal [IT] therapy in each course, plus ifosfamide, cytarabine, and etoposide alternating with cyclophosphamide and doxorubicin). Therapy for group non-B patients (lymphoblastic lymphoma and pleomorphic T-cell lymphoma [PTCL]) consisted of a Berlin-Frankfurt-Münster (BFM) acute lymphoblastic leukemia protocol, including cranial irradiation for advanced stage. Local therapy was restricted to patients with incomplete tumor regression. RESULTS: The probabilities of event-free survival (pEFS) at 7 years were 80% +/- 2% for the whole group, 81% +/- 3% for group B (n = 225), and 78% +/- 5% for group non-B (n = 77) with a follow-up duration of 3.6 to 7 years (median 5 years). Treatment results were comparable between NHL subtypes, except for PTCL, in which three of four patients suffered from relapse. Local disease manifestations were the most frequent site of failure. CONCLUSION: This therapy strategy provided patients of all NHL subtypes with an equally high chance to survive event-free, except patients with PTCL. With reduced systemic failure, local tumor control may become more important.
Adolescent↗
[Infectious diseases in oncologic patients].
Explore the source record for details and available documents.
Bacterial Infections↗
Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86.
In trial ALL-BFM 86, the largest multicenter trial of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight-drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD-cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety-eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.
Adolescent↗
Job task and psychosocial risk factors for work-related musculoskeletal disorders among newspaper employees.
OBJECTIVES: A cross-sectional study was conducted to assess the association of upper extremity musculoskeletal disorders and work-related factors among employees using video display terminals at a large metropolitan newspaper. METHODS: The study included 1050 randomly selected workers from four departments. The workers were asked to complete questionnaires on symptoms, job tasks, and psychosocial and work organization conditions. Musculoskeletal disorders of the upper extremities were defined by frequency, duration, and intensity of symptoms not attributable to acute injury. Data were analyzed with the use of logistic regression. RESULTS: A total of 973 workers completed the survey. The one-year period prevalence rate for any musculoskeletal disorder of the upper extremities was 41%. Neck symptoms (26%) were the most frequently reported, followed by hand or wrist (22%), shoulder (17%), and elbow (10%) symptoms. Greater time working at the video display station was associated with increased hand or wrist symptoms in a dose-response relationship. In addition, variables corresponding to increased work-load demands (eg, increased time working under deadline and increased job pressure) were associated with increased neck, shoulder, and hand or wrist disorders. Women were more likely to report symptoms in several areas, but this finding may reflect the concentration of women in jobs involving more risk factors. CONCLUSIONS: The results suggest a high prevalence of musculoskeletal disorders of the upper extremities among newspaper employees, and they provide additional evidence that increased work load, time pressure, and greater hours of computer use are related to the occurrence of work-related musculoskeletal disorders among these workers, particularly for disorders in the hand or wrist area.
Adult↗
[Why do we need therapy studies?].
Explore the source record for details and available documents.
Case-Control Studies↗
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↗