Three-dimensional visualization of pulmonary thromboemboli in chronic thromboembolic pulmonary hypertension with multiple detector-row spiral computed tomography.
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Biomedical subjects
Publications and source records attributed to C Scholten.
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The present study was performed to assess the difference in acceptance of psychosocial counseling and resulting benefits between patients with breast cancer with early or late onset. In a prospective randomized controlled study conducted over 6 months, 41 women with a new diagnosis of early breast cancer (group 1) and 43 patients with advanced breast cancer (group 2) received individually tailored psychosocial support and were compared against controls. This therapy was free of charge, and the duration of support was determined by the patients' wishes and needs. Among the patients with new onset of disease acceptance of the psychosocial counseling was high, and these patients experienced significant improvements in their quality of life. In contrast, acceptance of psychosocial counseling was low in the advanced breast cancer group and the therapy did not improve quality of life over the observation period of 6 months. Early psychosocial support in patients with breast cancer meets with a high acceptance rate and improves quality of life.
OBJECTIVE: To assess the sustainable benefits of a professional, multidisciplinary training program for patients with rheumatoid arthritis. DESIGN: Two studies with different observation periods. Study I was a prospective, randomized trial for 1 year. Study II was a noncontrolled observation over 5 years. SETTING: The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists, orthopedists, physicotherapists, psychologists and social workers. PATIENTS: Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year. INTERVENTIONS: The program covered the following fields: pathogenesis of rheumatoid arthritis, drug therapy, physicotherapy, practical exercise in remedial gymnastics, use of joint protection devices, orthopedic perspectives, psychological counseling, dietetics, information about unproven cures and social assistance. MAIN OUTCOME MEASURES: Clinical outcome was assessed by self-report questionnaires: (1) Stanford Health Assessment Questionnaire, (2) Freiburg Questionnaire of Coping with Illness, (3) Beck Depression Inventory, and (4) a 21-point scale to evaluate cognitive-behavioral and environmental impact. RESULTS: A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial. Between the end-point of the 1-year study and the 5-year evaluation, this improvement increased even more for functional status and coping with illness, whereas depression returned to baseline values. These effects were seen even without reinforcement of the training. CONCLUSION: A professional, multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy.
PURPOSE: (1) Quantification of minimal residual disease (MRD) by competitive CBFbeta/MYH11 reverse-transcriptase polymerase chain reaction (RT-PCR) in patients with acute myeloid leukemia (AML) and inversion(16) [inv(16)] during postremission therapy, (2) comparison of this method with conventional two-step RT-PCR, and (3) evaluation of a potential prognostic value. PATIENTS AND METHODS: MRD of six consecutive adult patients with AML and inv(16)(p13;q22) or t(16;16)(p13;q22) who entered complete remission (CR) was monitored by competitive CBFbeta/MYH11 RT-PCR in their bone marrow (BM) during postremission therapy with high-dose cytarabine (HiDAC) or after BM transplantation with a matched unrelated-donor marrow (MUD-BMT) during an observation period of 4.5 to 27 months after initiation of treatment. RESULTS: Competitive PCR showed a gradual decline by at least 4 orders of magnitude after 7 to 9 months in patients in continuous CR (CCR), while one patient who relapsed after 13.5 months only achieved a reduction by 2 orders of magnitude at the end of consolidation therapy. A rapid decrease below the detection limit was observed within 1 month in two patients after MUD-BMT. A temporary reappearance of molecular MRD was observed in these patients during immunosuppression for graft-versus-host disease (GvHD). After reduction of immunosuppression, the level of MRD dropped again below the PCR detection limit. Molecular monitoring by conventional two-step RT-PCR yielded comparable results only when multiple assays per time point were performed, while single-assay RT-PCR gave misleading results. CONCLUSION: Competitive RT-PCR is a valuable tool for molecular monitoring during postremission chemotherapy, as well as after BMT.
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OBJECTIVE: To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. METHODS: Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. RESULTS: Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. CONCLUSION: Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.
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The polymerase chain reaction (PCR) has revolutionized the diagnosis of leukemias, lymphomas and solid tumors over the past 10 years. This molecular method can amplify tumorspecific DNA or RNA markers by a factor of up to 1 x 10(6). Clinical applications include: (1) improvement of histologic diagnosis through the detection of clonality and definition of molecular markers specifically associated with certain disease; (2) prognostic assessment at diagnosis, with impact on initial therapeutic decisions; (3) monitoring of minimal residual disease and early detection of impending relapse after chemotherapy or bone marrow transplantation; (4) detection of residual tumor cells in bone marrow and peripheral blood stem cell harvests; (5) diagnosis of hereditary tumor syndromes. A number of these PCR assays is already incorporated in routine laboratory diagnostic procedures, especially in acute and chronic leukemias. The final goal of the clinical application of PCR is the development of risk adapted therapeutic concepts for neoplastic disease.
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We have compared the kinetics of minimal residual disease (MRD) by simultaneous polymerase chain reaction (PCR) monitoring with oligonucleotides for the immunoglobulin heavy chain (IgH) complementarity-determining region 3 (CDR3) and the T-cell receptor gamma chain gene (TCR gamma), as well as clone-specific CDR3 sequences in adult patients (aged 17-51 years) with acute lymphoblastic leukemia (ALL) who entered a complete hematological remission (CR) after chemotherapy with the German multicenter ALL (GMALL) protocol. The sensitivities were one in 10(2-3) for the CDR3- and TCR gamma-PCR and one in 10(5-6) for a two-step, seminested CDR3/clone-specific PCR. At diagnosis, 7/7 patients were CDR3 positive and four were TCR gamma positive in their bone marrow (BM). At the end of induction therapy (after 2 months) 4/6 tested positive for CDR3, 2/6 for TCR gamma, and 5/6 for clone-specific rearrangements. At the end of consolidation treatment (after 7 months) only 1/7 remained positive for CDR3, 2/7 for TCR gamma, and 5/7 for clone-specific rearrangements. After an observation period of 18-36 months, 4/7 patients were still in CR and all were PCR negative by the clone-specific method during or after maintenance therapy. Two patients died in leukemic relapse; one patient relapsed but is still alive. All three of these patients remained PCR positive throughout the course of their disease. Clonal evolution in the IgH locus was found in one of these patients. We conclude that the molecular response to chemotherapy in adult B-lineage ALL is slow, even in patients without risk factors other than age. As in childhood ALL, most patients with long-term CR convert to PCR negativity approximately 18 months after the start of chemotherapy. The data also suggest the existence of early clone-specific PCR negativity in a small proportion of long-term survivors. The predictive value of this observation will now have to be confirmed in a larger study.
Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.
Due to the relatively low tumour cell contamination of peripheral blood in patients with multiple myeloma, autologous transplantation of circulating stem cells may have theoretical advantages over autologous bone marrow transplantation. In four patients with multiple myeloma who where considered potential candidates for autologous stem cell transplantation G-CSF (600 micrograms/day) was administered following chemotherapy in order to maximally increase the number of circulating progenitor cells during haematopoietic rebound and to facilitate progenitor cell harvest by leukapheresis. In two previously untreated patients the administration of G-CSF following chemotherapy according to the UVA protocol (ultralan, vincristine, adriamycin) greatly increased circulating haematopoietic stem cells from 247 to 7552 CFU-GM/ml in patient 1 and from 173 to 6361 CFU-GM/ml in patient 2, which by far exceeded the increase in progenitor cells following chemotherapy alone, namely only to 594 and 317 CFU-GM/ml in patient 1 and patient 2, respectively. In two repeatedly pretreated patients, the combination of UVA and G-CSF was much less effective. Progenitor cells increased from 144 to 735 CFU-GM/ml in patient 3 and only from 222 to 232 CFU-GM/ml in patient 4. In both cases, however, mobilization of haematopoietic progenitor cells by G-CSF following cyclophosphamide (50 and 70 mg/kg body weight, respectively) led to much higher CFU-GM peak values (5324 in patient 3 and 2245 in patient 4), thus allowing an adequate harvest of mononuclear cells and CD 34+ cell numbers to achieve, in all probability, the prompt and complete reconstitution of haematopoiesis in case of transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of adjuvant treatment with tamoxifen on recurrence and survival rates was determined in a prospective randomized trial in 98 postmenopausal women (mean age 62.7 [49-77] years) with lymph node-negative breast cancer who had undergone modified radical mastectomy with axillary lymphadenectomy. The tamoxifen group (n = 48) received 10 mg of the drug twice daily for one year. After a mean period of 8 (6-11) years the tamoxifen group had a significantly higher rate of survival without recurrence than the control (no tamoxifen) group (83% vs 61.5%, P = 0.02) and a higher overall survival rate (95% vs 81.9%, P = 0.05). These results indicate that adjuvant tamoxifen favourably influences the prognosis for postmenopausal women with lymph node-negative breast cancer after radical mastectomy with axillary lymphadenectomy.
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We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.