We evaluated the infusion-related toxicity of cryopreserved autologous circulating progenitor cells transplanted in 22 patients receiving high dose chemotherapy and stem cells transplantation for ...malignancy.
Progenitor cells were collected following mobilization with chemotherapy plus filgrastim and stored in liquid nitrogen in the presence of 10% dimethylsulfoxide (DMSO). Before infusion of the graft, patients were medicated with mannitol, hydrocortisone and clorphenamine. The amount of DMSO infused as well as the number of dead and damaged cells were evaluated as possible cause of toxicity.
Eleven patients (50%) experienced symptoms related to graft infusion, nausea and vomiting being the most common adverse events. Hypotension was documented in 3 patients (one of them developing transient bradycardia resolved with atropin administration) and one had hypertension with tachycardia. Other observed side effects were: chest tightness (2 pts), fever and chills (3 pts), associated with abdominal cramps (2 pts). 7 out of 8 (88%) patients infused with greater than 30 mL volume of DMSO experienced side-effects, the grade of toxicity being significantly less in those receiving lower amount (< 30 mL) of DMSO. Two out of 4 pts who received the highest number of dead cells (> 10 x 10(9)) developed toxicity.
In our experience the infusion of cryopreserved peripheral blood progenitors caused minor to moderate toxicity in most cases and, when present, side effects were observed only during infusion. The amount of DMSO present in the graft is related to the grade of toxicity.
Endoscopic ultrasonography, both conventional and interventional, has been used increasingly during the past 20 years and is deemed a safe technique. Its complication rate, however, has been studied ...to only a limited extent. This multicentre investigation sought to establish the complication rate for a large number of endoscopic ultrasonography procedures.
By means of a questionnaire, we collected data from six centres on the number of endoscopic ultrasonography examinations performed and divided them into conventional and interventional examinations of the upper and lower gastrointestinal tract. Information was obtained on technical modalities such as instruments and sedation and, for interventional endoscopic ultrasonography, indications, pre-procedural exams and technical details (needle calibre, number of passes) had to be specified. Complications were classified as mild, moderate, severe or fatal and their onset as immediate, early or late. Variables that entered into the analysis of complication rate included type of endoscopic ultrasonography instrument used, type and site of lesion biopsied, number of needle passes and operator experience.
Eleven thousand five hundred thirty nine endoscopic ultrasonographic procedures were reported, of which 10,731 were conventional and 808 interventional. No deaths occurred; there were 14 (0.12%) complications, 5 (0.046%) of them following conventional endoscopic ultrasonography and 9 (1.11%) after interventional endoscopic ultrasonography. Seven complications were mild, four moderate and three severe.
Both conventional and interventional endoscopic ultrasonography were confirmed to be acceptably safe techniques.
Fatty acid desaturation in plastids and chloroplasts depends on the electron-donor activity of ferredoxins. Using degenerate oligonucleotides designed from known photosynthetic and heterotrophic ...plant ferredoxin sequences, two full-length ferredoxin cDNAs were cloned from sunflower (Helianthus annuus L.) leaves and developing seeds, HaFd1 and HaFd2, homologous to photosynthetic and non-photosynthetic ferredoxins, respectively. Based on these cDNAs, the respective genomic sequences were obtained and the presence of DNA polymorphisms was investigated. Complete sequencing of the HaFd1 and HaFd2 genes in different lines indicated the presence of two haplotypes for HaFd2 and their alignment showed that sequence polymorphisms are restricted to the 5'-NTR intron. In addition, specific DNA markers for the HaFd1 and HaFd2 genes were developed that enabled the genes to be mapped. Accordingly, the HaFd1 locus maps to linkage group 10 of the public sunflower map, while the HaFd2 locus maps to linkage group 11. Both ferredoxins display different spatial-temporal patterns of expression. While HaFd2 is expressed at similar levels in all tissues tested (leaves, stem, roots, cotyledons and developing seeds), HaFd1 is more strongly expressed in green tissues than in all the other tissues tested. Both photosynthetic- and heterotrophic-ferredoxins are present in sunflower seeds and may contribute to fatty acid desaturation during oil accumulation. Nevertheless, the levels of HaFd2 expression during seed formation are distinct in lines that only varied in the HaFd2 haplotypes they expressed.
To elucidate the mechanism by which trastuzumab, a humanized monoclonal antibody against HER2 with proven survival benefit in women with HER2-positive metastatic breast cancer, mediates its antitumor ...activity.
A pilot study including 11 patients with HER2-positive tumors treated in a neo-adjuvant setting with trastuzumab was performed. Trastuzumab was administered i.v. at a dose of 4 mg/kg followed by three weekly i.v. doses of 2 mg/kg. The primary tumor was surgically removed 7 days after the last treatment. Surgical samples, tumor biopsies, and lymphocytes from these patients were collected for biological studies.
Clinical data indicated one complete pathological remission and four partial remissions using RECIST (Response Evaluation Criteria in Solid Tumors). Trastuzumab was well tolerated and neither serious adverse events nor changes in cardiac function were observed during this short-term treatment and after surgery. The biological data showed that, independent of response, (a) all patients showed high levels of circulating trastuzumab; (b) saturating level of trastuzumab was present in all of the tumors; (c) no down-modulation of HER2 was observed in any tumors; (d) no changes in vessel diameter was observed in any tumors; (e) no changes in proliferation was observed in any tumors; and (f) a strong infiltration by lymphoid cells was observed in all cases. Patients with complete remission or partial remission were found to have a higher in situ infiltration of leukocytes and a higher capability to mediate in vitro antibody-dependent cellular cytotoxicity activity.
The results of this pilot study argue against trastuzumab activity in patients through down-modulation of HER2 but in favor of antibody-dependent cellular cytotoxicity guiding efforts to optimize the use of trastuzumab in breast cancer patients.
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