Validation of BIOMED-2 multiplex PCR tubes for detection of TCRB gene rearrangements in T-cell malignancies.

The BIOMED-2 Concerted Action BMH4-CT98-3936 on 'Polymerase chain reaction (PCR)-based clonality studies for early diagnosis of lymphoproliferative disorders' developed standardized PCR protocols for detection of immunoglobulin (Ig) and T-cell receptor (TCR) rearrangements, including TCR beta (TCRB). As no comparable TCRB PCR method pre-existed and only a limited number of samples was tested within the BIOMED-2 study, we initiated this study for further validation of the newly developed TCRB PCR approach by comparing PCR data with previously generated Southern blot (SB) data in a series of 66 immature (ALL) and 36 mature T-cell malignancies. In 91% of cases, concordant PCR and SB results were found. Discrepancies consisted of either failure to detect SB-detected TCRB rearrangements by PCR (6.5%) or detection of an additional non-SB defined rearrangement (2.5%). In 99% of cases (99/100), at least one clonal TCRB rearrangement was detected by PCR in the SB-positive cases. A predominance of complete Vbeta-Jbeta rearrangements was seen in TCRalphabeta(+) T-cell malignancies and CD3-negative T-ALL (100 and 90%, respectively), whereas in TCRgammadelta(+) T-ALL, more incomplete Dbeta-Jbeta TCRB rearrangements were detected (73%). Our results underline the reliability of this new TCRB PCR method and its strategic applicability in clonality diagnostics of lymphoproliferative disorders and MRD studies.     

Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT. A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n = 15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary-artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (deltaO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively. A significant correlation between deltaO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p < 0.05). PGI2 treatment induced a significant decrease in deltaO2 after 24 and 48 h after reperfusion (p < 0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418 +/- 99 vs. 638 +/- 156 U/L, p < 0.1). These results suggest that administration of PGI2 after OLT improves hepatic-splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.     

CAD/CAM technology-elaboration of electronic model through optical impression in the fabrication of the dental prostheses by a computer assisted device

In modern CAD/CAM technology of dental prosthetics, the "optical impression" taken by special video cameras deploying 3D-recording of the oral situation (Cerec 1, Cerec 2) initiates the computer-generated production of a digital model. The computer receives and renders the digital data obtained through "optical impression" i.e. data acquisition not as a "negative" of the oral situation but as a "positive" copy of it, namely as a digital model in a virtual environment which can be displayed on the screen and be further used in the fabrication of dental prostheses by means of a computer-assisted device (CAM or CIM).     

Le syndrome de Smith-Magenis

Smith-Magenis syndrome is caused by a 17p11.2 deletion. It associates mental retardation, facial dysmorphism and brachydactyly; aberrant behavior and major sleep problems are present in 70% of the cases. It is probably under-diagnosed because the facial abnormalities are mild and the behavioral problems with hyperactivity and self-injuries are dominant, leading to the diagnosis of psychiatric pathology. However these behavioral problems are sufficiently characterized to allow the diagnosis of the syndrome and look for a 17p11.2 microdeletion. Otorhinolaryngologic, ophtalmologic, cardiac and renal abnormalities can be associated and their evaluation is necessary. Smith-Magenis syndrome is considered as a contiguous gene syndrome. Genes have been mapped and isolated to the critical region, but their participation in the pathogenesis of the syndrome remains unclear.     

Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study

Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC).Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m², leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m², weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m² was administered additionally on days 1 and 22, q 50 days.Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting.Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.     

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.