Zusammenfassung
Therapeutisches Wirken wird durch begünstigende Kontextfaktoren erleichtert, wobei therapeutische Interventionen gleichzeitig Anregung sein können, Kontextfaktoren zu verändern. ...Kommunikation und Therapie werden durch eine gute therapeutische Beziehung erst ermöglicht, vor allem unter erschwerten inneren und äußeren Bedingungen.
This 6th edition of the atlas has integrated the 2001 WHO classification and made use of figures and descriptions to document recently described types of leukemia and lymphoma. The latter include ...leukemias of dendritic cells, rare lymphomas and persistent polyclonal B lymphocytosis, which takes a special place in the classification. The volume covers all the microscopic methods in hematology that form the basis of diagnosis as well as the results of modern immunologic, cytogenetic and molecular-genetic investigation. Special emphasis is placed on the cytogenetic and molecular-genetic characterization of biological entities that might form the basis for innovative therapies. Normal results and pathological findings are compared, and the various findings made during therapy are depicted. All in all the Atlas of Clinical Hematology represents a complete and helpful reference work which should be present in every hematologic and oncologic department as well as in clinical laboratories for online diagnostics and scientific research.
Molecular and cellular basis of radiation fibrosis BURGER, A; LÖFFLER, H; BAMBERG, M ...
International journal of radiation biology,
04/1998, Letnik:
73, Številka:
4
Journal Article, Conference Proceeding
Recenzirano
Purpose: Recent data from the literature and the experimental work of the authors clearly indicate that TGF- beta 1 is a key modulator of cellular events, for example, induction of terminal ...differentiation, resulting in radiation-induced fibrosis. Therefore, the present study analysed which cellular processes induced by exogeneously added TGF- beta could be responsible for the induction, development and manifestation of the fibrotic phenotype in culture. Materials and methods: Rat lung fibroblast cultures (passage 1) were used. As a function of treatment with TGF- beta and/or anti-TGF beta -antibody, the clonogenic activity and differentiation pattern were analysed by colony-formation assays. Results: It could be demonstrated that treatment of rat lung progenitor fibroblasts with TGF- beta 1 resulted in a pronounced shift in the differentiation pattern, i.e. induction of post-mitotic fibrocytes. This TGF- beta 1-dependent terminal differentiation could be abolished by simultaneous treatment with a neutralizing antibody directed against TGF- beta 1. Conclusions: The data presented indicate that TGF- beta 1 is one major candidate mediating the accelerated terminal differentiation of progenitor fibroblasts to post-mitotic functional fibrocytes, which results in the fibrotic phenotype of this cell system.
Mutations in mismatch repair (MMR) genes result in microsatellite instability (MSI) and early onset of colorectal cancer. To get mechanistic insights into the time scale, sequence and frequency of ...intestinal stem cell (ISC) transformation, we quantified MSI and growth characteristics of organoids of Msh2-deficient and control mice from birth until tumor formation and related them to tissue gene expression. Although in Msh2-deficient organoids MSI continuously increased from birth, growth characteristics remained stable at first. Months before tumor onset, normal Msh2-deficient tissue contained tumor precursor cells forming organoids with higher MSI, cystic growth and growth rates resembling temporarily those of tumor organoids. Consistently, Msh2-deficient tissue exhibited a tumor-like gene signature. Normal Msh2-deficient organoids showed increased inheritable transient cyst-like growth, which became independent of R-spondin. ISC transformation proceeded faster in vitro than in vivo independent of the underlying genotype but more under MMR deficiency. Transient cyst-like growth but not MSI was suppressed by aspirin. In summary, as highlighted by organoids, molecular alterations continuously proceeded long before tumor onset in MMR-deficient intestine, thus increasing its susceptibility for ISC transformation.
Summary
Background : Symptoms of irritable bowel syndrome are often cyclical and thus may require repeated rather than continuous therapy. Tegaserod is effective and well‐tolerated for irritable ...bowel syndrome with constipation but data on retreatment are lacking.
Aim : To assess whether tegaserod retreatment is as efficacious and well‐tolerated as initial treatment in a primary care setting.
Methods : This open‐label trial was designed to evaluate the effectiveness of tegaserod under real‐life conditions. Irritable bowel syndrome with constipation patients received tegaserod 6 mg b.d. for 12 weeks; response was assessed at weeks 4 and 12. Responders (those achieving satisfactory relief for at least 2 of the previous 4 weeks) at weeks 4 and/or 12 entered an 8‐week withdrawal period where symptom recurrence was assessed. Patients experiencing recurrence could receive tegaserod 6 mg b.d. for another 4 weeks (retreatment phase) and on completion, could choose to continue tegaserod in a 6‐month extension study.
Results : A total of 513 patients received initial treatment with tegaserod; 85.0% (436 of 513) responded. 403 responders entered the withdrawal period; symptoms recurred in 83.9% (338 of 403) after a mean of 38 days. Of the 307 patients who subsequently entered retreatment 89.3% (274 of 307) responded. Among patients entering the retreatment period, 269 (87.6%) had responded within the first 4 weeks of initial treatment. Of these, 243 (90.3%) responded to tegaserod retreatment. Adverse events were infrequent and similar during 4 weeks of the initial treatment period (11.1%) and on retreatment (10.4%). The extension study, completed by 188 of 232 (81.0%) patients, demonstrated good long‐term tolerability of tegaserod.
Conclusions : Irritable bowel syndrome with constipation patients can be successfully treated, and retreated, with tegaserod 6 mg b.d. Tegaserod was well‐tolerated during initial and retreatment periods.
Summary
Background When evaluating transepidermal water loss (TEWL) in patch testing, the occlusive effect of the patch must be considered as an important artificial impairment of the measurement.
...Objectives To investigate the time course of effects of occlusion.
Methods Epicutaneous patches with sodium lauryl sulphate (SLS) 0·25%, SLS 0·5%, water and an empty test chamber (control) were applied on the volar forearm for different time intervals (12, 24, 48 h). Test reactions were evaluated by measurement of TEWL immediately, every 15 min during the first hour, every 30 min during the following 3 h and 24 h after patch removal.
Results After patch removal, TEWL values showed a steep increase. When compared with basal values, TEWL values after SLS patch testing remained increased for 24 h, whereas TEWL values on water patch sites were only significantly increased for up to 180 min, and on empty patch sites for only up to 120 min after patch removal. The prolonged increase in TEWL values in SLS patch testing seemed to be induced by barrier function damage caused by SLS itself, as shown in various earlier studies. After the initial increase, TEWL values showed a significant decrease for all patches from 0 to 120 min after patch removal. Patch testing with water gave a significant decrease in TEWL values up to 180 min, and for empty chambers (control) up to 150 min after removal of patches. These data suggest that the occlusive effect on TEWL in patch testing ends 3 h after the removal of test chambers.
Conclusions We recommend TEWL measurement in SLS patch testing after a period of at least 3 h after patch removal. For practical purposes a 24‐h period after patch removal may be useful.
Background: The influence of nutrition on the physiological functions of man is well studied. Numerous diseases can be exacerbated by obesity. However, it has not yet been determined whether body ...weight and body mass index (BMI), as an indicator of a high body fat store, can influence skin sensitivity.
Objective: This study investigates the correlation between body mass index and the epidermal functions, evaluated by bioengineering methods, before and after an irritant patch test with sodium lauryl sulphate (SLS).
Methods: Epidermal functions were evaluated using an evaporimeter, chromameter and laser‐Doppler‐flowmeter. Patch testing was conducted for 48 h with two different concentrations of SLS (0.25% and 0.5%) on the forearms of healthy volunteers. Measurements were performed 24 h after patch removal.
Results: Obese individuals showed significantly increased transepidermal water loss (TEWL), skin blood flow and skin colour (red) as compared to a control group. However, the degree of skin sensitivity to SLS was not correlated with BMI.
Conclusion: Basal biophysical parameters of the skin are primarily correlated with the BMI. This may be caused by obesity‐induced physiological changes, e.g. increased sweat gland activity, high blood pressure and physiological temperature‐regulating system. The epidermal barrier function, as evaluated after SLS patch testing is, however, not correlated with a high BMI, indicating a normal skin barrier.
The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, ...we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA ...in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June 1999, were evaluated. The median age was 43 (16-60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were > or =5 x 10(9)/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARalpha transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARalpha (sensitivity 10(-4)) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.
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