Value of various amino acid mixtures for the treatment of chronic liver damage

A reproducible liver lesion was caused in 28 pigs by intermittent, intraperitoneal administration of thioacetamide. The morphological degree of the liver lesion was checked by histological investigations (material drawn from the liver by biopsy). During a 3-day infusion period a so-called liver solution (Aminofusin hepar) was given to one group of animals, a normal solution (Infesol) to a second group, and only an electrolyte infusion solution under oral nutrition ad libitum to a third one. The solutions were labelled with (15N) glycine. The amounts of total N, total 15N, 15N with single non-protein fractions, a number of enzymes of 15N incorporated into the liver protein were measured in urine, and the following points were established: 1. The catabolic situation of metabolism is eliminated both by the so-called normal solution and the specific amino acid solution. The two mixtures of L-amino acids thus have a nutritive effect. 2. The toxic liver lesion is an indication for parenteral nutrition. Oral nutrition alone is not sufficient. 3. The so-called liver solution influences the liver metabolism of the protracted liver lesion more than the so-called normal solution does, and considerably more than an electrolyte infusion solution under oral nutrition ad libitum.     

The atopy patch test -- reproducibility and comparison of different evaluation methods

BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.     

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.     

Cologne high-dose sequential chemotherapy in relapsed and refractory Hodgkin lymphoma: results of a large multicenter study of the German Hodgkin Lymphoma Study Group (GHSG).

BACKGROUND: We designed a dose- and time-intensified high-dose sequential chemotherapy regimen for patients with relapsed and refractory Hodgkin lymphoma (HD). PATIENTS AND METHODS: Eligibility criteria included age 18-65 years, histologically proven primary progressive (PD) or relapsed HD. Treatment consisted of two cycles DHAP (dexamethasone, high-dose cytarabine, cisplatinum); patients with chemosensitive disease received cyclophosphamide followed by peripheral blood stem cell harvest; methotrexate plus vincristine, etoposide and BEAM plus peripheral blood stem cell transplantation (PBSCT). RESULTS: A total of 102 patients (median age 34 years, range 18-64) were enrolled. The response rate was 80% (72% complete response, 8% partial response). With a median follow-up of 30 months (range 3-61 months), freedom from second failure (FF2F) and overall survival (OS) were 59% and 78% for all patients, respectively. FF2F and OS for patients with early relapse were 62% and 81%, for late relapse 65% and 81%; for PD 41% and 48%, and for multiple relapse 39% and 48%, respectively. In multivariate analysis response after DHAP (P <0.0001) and duration of first remission (PD and multiple relapse versus early and late relapse; P=0.0127) were prognostic factors for FF2F. Response after DHAP (P <0.0081), duration of first remission (P=0.0017) and anemia (P=0.019) were significant for OS. CONCLUSION: Based on the promising results of this study, a prospective randomized European intergroup study was started comparing this intensified regimen with two courses of DHAP followed by BEAM (HD-R2 protocol).     

The Impact of Neurochemical Mediators on Antidepressant Effectiveness

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Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition

Cutaneous melanoma is a tumor with rising incidence and a very poor prognosis at the disseminated stage. Melanomas are characterized by frequent mutations in BRAF and also by overexpression of fibroblast growth factor 2 (FGF2), offering opportunities for therapeutic intervention. We investigated inhibition of FGF signaling and its combination with dacarbazine or BRAF inhibitors as an antitumor strategy in melanoma. The majority of melanoma cell lines displayed overexpression of FGF2 but also FGF5 and FGF18 together with different isoforms of FGF receptors (FGFRs) 1-4. Blockade of FGF signals with dominant-negative receptor constructs (dnFGFR1, 3, or 4) or small-molecule inhibitors (SU5402 and PD166866) reduced melanoma cell proliferation, colony formation, as well as anchorage-independent growth, and increased apoptosis. DnFGFR constructs also significantly inhibited tumor growth in vivo. Combination of FGF inhibitors with dacarbazine showed additive or antagonistic effects, whereas synergistic drug interaction was observed when combining FGFR inhibition with the multikinase/BRAF inhibitor sorafenib or the V600E mutant-specific BRAF inhibitor RG7204. In conclusion, FGFR inhibition has antitumor effects against melanoma cells in vitro and in vivo. Combination with BRAF inhibition offers a potential for synergistic antimelanoma effects and represents a promising therapeutic strategy against advanced melanoma.