Spinal osteomyelitis due to <Emphasis Type="Italic">Aspergillus flavus</Emphasis> in a child: a rare complication after haematopoietic stem cell transplantation

We report the case of a child affected by acute myeloid leukaemia who was treated with allogeneic haematopoietic stem cell transplantation and developed cervicothoracic spinal osteomyelitis due to Aspergillus flavus. The diagnosis was difficult on a clinical basis, but made possible by conventional radiography and MRI.     

Ecophysiological requirements and survival of a Trichoderma atroviride isolate with biocontrol potential

Trichoderma atroviride SC1, isolated from decayed hazelnut wood in northern Italy in 2000, is a promising fungal agent for biological control of soil-borne plant pathogens. The objective of this research was to characterize the biology and ecology of this fungus, in order to determine its environmental parameter tolerance levels and its behavior in the phylloplane and soil systems. To better characterize T. atroviride SC1, the influences of pH, temperature, water activity and different nitrogen and carbon sources on its in vitro growth were evaluated. T. atroviride SC1 survival was assessed on strawberry leaves under controlled conditions in a greenhouse and in sterilized and non-sterilized soil samples kept at room temperature. Results showed that isolate SC1 is mesophilic and grows best at 25 degrees C. The fungus tolerates a wide range of pH levels, but growth was reduced on alkaline media (pH >or= 8). The nitrogen and carbon sources peptone, tryptone, nitrate, mannose, galactose and sucrose were associated with the highest mycelial biomass production, as compared with other potential sources of nitrogen and carbon. The fungus survived on strawberry leaves under greenhouse conditions (25 +/- 2 degrees C, RH = 60 +/- 10%) and grew in sterilized soils at room temperature (23 +/- 2 degrees C) for 45 d. However, no increase in mycelial dry weight was observed in non-sterilized soils. T. atroviride SC1 survived under the test conditions, showing a good potential for use in soil and foliar biocontrol applications.     

Anti-tumor immunotherapy against multidrug resistance

Overexpression of a membrane glycoprotein (P170) represents the most common multidrug resistance (MDR) mechanism in cancer therapy. Specific autoantibodies to extracellular loops 1, 2 and 4 of murine P170 are elicited in mice using palmitoylated synthetic peptides reconstituted in liposomes with or without Lipid A and resuspended in alum. IgM antibodies are detected 14 days following the first injection and IgG1 become predominant after the third challenge. Animals do not show any autoimmunity symptoms or induced toxicity up to 18 months after the immunization. Previous immunizations of mice using liposomes with mdr1 peptides efficiently improve chemotherapy with doxorubicin and vinblastine against P388 R cells with a 77% increase of survival half time in the immunized group. Sera from immunized mice are also effective in reducing cellular resistance to vinblastine and doxorubicin in vitro. Taken together these data suggest that this immunization approach might have potential clinical applications.     

3D optoelectronic analysis of interfractional patient setup variability in frameless extracranial stereotactic radiotherapy

PURPOSE: To investigate size and frequency of interfractional patient setup variability in hypofractionated stereotactic extracranial radiotherapy. METHODS AND MATERIALS: Infrared optical 3D tracking of surface markers was applied to quantify setup variability on 51 patients. Isocenter position repeatability was assessed by means of frameless anatomic calibration and was compared with portal image evaluation. Specific data analysis allowed for compensation of patients' breathing movements and for separation of the effects of operator-dependent misalignments and respiration-induced displacements. Effects of patient position (supine vs. prone) and treatment table configuration were investigated. RESULTS: Patient positioning assisted by the optical tracking device allowed reducing displacements of surface control points within the 3-mm range. Errors in isocenter localization were in the range of a few millimeters. This was in agreement with the portal image evaluation. Breathing motion introduced appreciable errors, which increased control points and isocenter 3D variability. This effect was significantly higher than those related to other investigated factors. CONCLUSIONS: The role of infrared optical tracking devices for patient positioning is assessed on a large patient population. Their use in the frame of high-precision radiotherapy is emphasized by the application of related methodologies for breathing phase detection and frameless isocenter localization.     

VEGF-D is expressed in activated lymphoid cells and in tumors of hematopoietic and lymphoid tissues

Vascular Endothelial Growth Factor (VEGF)-D is a member of the VEGF family of angiogenic growth factors that activate the Vascular Endothelial Growth Factor Receptor (VEGFR)-2 and VEGFR-3, which are mainly expressed in blood and lymphatic vessels. Here we have analyzed by using monoclonal antibodies, the expression of VEGF-D and its cognate receptor VEGFR-3 in normal and pathologic bone marrow and lymph node biopsies. This analysis revealed that VEGF-D is expressed in B cells of the germinal centers, scattered B and T blasts, myeloid progenitors, acute leukemia, several types of non Hodgkin lymphoma, and classical Hodgkin's lymphoma. In normal tissues VEGFR-3 was only expressed in fenestrated capillaries of bone marrow and in lymphatic vessels of lymph nodes, while in VEGF-D expressing tumors newly formed vessels, but not malignant cells, showed high VEGFR-3 expression. These data suggest that VEGF-D could contribute to leukemia and lymphoma growth via the induction of angiogenesis in bone marrow and lymphoid tissues.     

Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma

BACKGROUND: The objective of the current study was a retrospective evaluation of 100 consecutive premenopausal women with high-risk, early breast carcinoma who received a gonadotropin-releasing hormone (Gn-RH) analogue as ovarian protection during adjuvant chemotherapy. METHODS: After surgery, patients received a Gn-RH analogue and adjuvant chemotherapy, which was tailored to their peculiar biologic features. The median patient age was 43 years (range, 27-50 yrs). Fifty-two women had positive estrogen receptor (ER) status, and 48 women had negative ER status. There were 64 women with Stage II breast carcinoma and 36 women with UICC Stage III breast carcinoma. All patients had their serum estradiol suppressed to values<40 pg/mL. The chemotherapy regimens administered included cyclophosphamide, methotrexate, and 5-fluorouracil (n=26 patients) and anthracycline-based regimens (n=74 patients, including 9 patients who had >10 positive axillary lymph nodes, who also received high-dose chemotherapy with autologous peripheral blood progenitor cell transplantation). Patients with positive c-erb-2 status also received a taxane. Eighty patients received radiation therapy. During therapy with the Gn-RH analogue, patients who had a positive ER status after chemotherapy received an aromatase inhibitor. RESULTS: After a median follow-up of 75 months, normal menses were resumed by all patients younger than age 40 years and by 56% of patients older than age 40 years. Three pregnancies were observed that resulted in two normal deliveries and one voluntary abortion. The projected recurrence-free survival rates at 5 years and 10 years were 84% and 76%, respectively; and the projected overall survival rates at 5 years and 10 years were 96% and 91%, respectively. CONCLUSIONS: The current data showed that, in premenopausal women with early breast carcinoma, the addition of a Gn-RH analogue to adjuvant therapy and temporary total estrogen suppression in patients with ER-positive disease was tolerated well, protected long-term ovarian function, and appeared to improve the expected clinical outcome.     

Real-time in vivo dosimetry using micro-MOSFET detectors during intraoperative electron beam radiation therapy in early-stage breast cancer.

PURPOSE: In a previous paper we reported the results of off-line in vivo measurements using radiochromic films in IOERT. In the present study, a further step was made, aiming at the improvement of the effectiveness of in vivo dosimetry, based on a real-time check of the dose. MATERIALS AND METHODS: Entrance dose was determined using micro-MOSFET detectors placed inside a thin, sterile, transparent catheter. The epoxy side of the detector was faced towards the beam to minimize the anisotropy. Each detector was plugged into a bias supply (standard sensitivity) and calibrated at 5 Gy using 6 MeV electrons produced by a conventional linac. Detectors were characterized in terms of linearity, precision and dose per pulse dependence. No energy and temperature dependence was found. The sensitivity change of detectors was about 1% per 20 Gy accumulated dose. Correction factors to convert surface to entrance dose were determined for each combination of energy and applicator. From November 2004 to May 2005, in vivo dosimetry was performed on 45 patients affected by early-stage breast cancer, who underwent IOERT to the tumour bed. IOERT was delivered using electrons (4-10 MeV) at high dose per pulse, produced by either a Novac7 or a Liac mobile linac. RESULTS: The mean ratio between measured and expected dose was 1.006+/-0.035 (1 SD), in the range 0.92-1.1. The procedure uncertainty was 3.6%. Micro-MOSFETs appeared suitable for in vivo dosimetry in IOERT, although some unfavourable aspects, like the limited lifetime and the anisotropy with no build-up, were found. Prospectively, a real-time action level (+/-6%) on dose discrepancy was defined. CONCLUSIONS: Excellent agreement between measured and expected doses was found. Real-time in vivo dosimetry appeared feasible, reliable and more effective than the method previously published.