A new tool for assessing the risk of fall in children with severe disability: development of the ALICE scale.

Introduction: It is known in the literature that the main cause of physical impairment in children with severe disabilities is falling, which can worsen their already compromised condition. There are no specific scales for this population in the literature, neither in Italian nor in other languages. We created and validated a scale for assessing the risk of falling in children with severe disabilities. Study design: Observational prospective study. Methods: We enrolled children (inpatients or day-hospital) admitted to the "Santa Maria Bambina Centre" of the "Fondazione Onlus Sacra Famiglia" in Cesano Boscone, Milan; the Content Validity Index of the Scale was calculated to assess the content validity of a new scale (ALICE). Cronbach's alpha coefficient (α) was used to examine internal consistency, Spearman's rho coefficient to test inter-rater reliability. Sensitivity, specificity, positive and negative predictive values were calculated. Results: Out of 48 patients enrolled, 14 fell (29.2%). The ALICE scale, with cut-off set at 16, showed a sensitivity of 100%, a specificity of 88.2%, a positive predictive value of 77.8% and a negative predictive value of 100%. The Content Validity Index of the Scale (=0.93), inter-rater reliability (rho=0.91, p<0.001) and Cronbach's alpha (=0.72) were satisfactory. Conclusions: The ALICE scale seems reliable and valid in the disabled population and can be applied by nurses. Further studies with larger samples and a multicentre design are needed.

CyberKnife robotic image-guided stereotactic radiotherapy for oligometastic cancer : A prospective evaluation of 95 patients/118 lesions.

PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray Inc. Sunnyvale, USA)-based stereotactic radiotherapy (CBK-SRT) for oligometastic cancer patients. PATIENTS AND METHODS: Between May 2007 and December 2009, 95 patients with a total of 118 lesions underwent CBK-SRT (median dose 24 Gy in 3 fractions). INCLUSION CRITERIA: adult patients with limited volume cancer; suitability for SRT but not for other local therapies. Primary diagnoses included breast, lung, head and neck, gastrointestinal and other malignancies. Prostate cancer patients were excluded. Concomitant systemic therapy was given in 40 % of cases and median follow-up was 12 months. Toxicity and tumor response were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale and Response Evaluation Criteria in Solid Tumors RECIST. RESULTS: Toxicity was rare and observed mainly in patients with comorbidities or uncontrolled cancer. Out of 87 evaluable lesions, complete radiological response, partial response, stabilization and progressive disease were observed in 15 (17 %), 25 (29 %), 34 (39 %) and 13 (15 %) lesions, respectively. Upon restricting the analysis to lesions treated with CBK-SRT alone (no concomitant therapy), response- and local control (LC) rates remained similar. Actuarial 3-year in-field progression-free survival- (i.e. LC), progression-free survival- (PFS) and overall-survival (OS) rates were 67.6, 18.4, and 31.2 %, respectively. LC was reduced in cases of early recurrence. OS- and cause-specific survival (CSS) rates were significantly lower in patients treated for visceral lesions. Failures were predominantly out-field. CONCLUSION: CBK-SRT is a feasible therapeutic approach for oligometastastic cancer patients that provides long-term in-field tumor control with a low toxicity profile. Further investigations should focus on dose escalation and optimization of the combination with systemic therapies.

Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: using a three-dimensional tool to evaluate the first level coverage of the axillary nodes.

Recent data show that axillary coverage can be obtained, but only through a selective CT-based treatment planning, as standard tangential fields are inadequate to deliver therapeutic doses. Currently, the replacement of axillary dissection with new techniques, such as sentinel node (SN) biopsy, makes it necessary to re-address the question about the real role of axillary irradiation, complicated by the differences in the anatomy of dissected and undissected axillary regions. The purpose of this paper is the dosimetric analysis of first axillary level coverage in standard irradiation of 15 breast-cancer patients treated with quadrantectomy and SN biopsy (negative finding). During surgery a clip on the site of the SN was positioned, marking the caudal margin of first axillary level. After the breast treatment plan was completed, the first axillary level was contoured on CT scans, from the site of the surgical clip up to the sternal manubrium, for coverage analysis with dose-volume histograms (DVHs) and three-dimensional isodose visualization. The maximum dose mean ranged from 5% to 80% of the prescribed dose (mean value 48.7%). The mean total dose received by the volume of interest was lower than 40 Gy in all but one patient. No patient had total irradiation of first nodal level; only one patient had 35% of the volume enclosed in the 100% isodose. Our analysis lead to the conclusion that therapeutic doses are not really delivered to first level axillary level nodes by a standard tangential field technique, and that specific treatment planning and beam arrangement are required when adequate coverage is necessary.

Fas ligand is up-regulated during the colorectal adenoma-carcinoma sequence.

AIMS: Fas ligand (FasL) expression by cancer cells may mediate tumour immune privilege. The purpose of the present study was to investigate the timing and significance of FasL expression during the colorectal adenoma-carcinoma sequence. METHODS: FasL expression was studied by immunohistochemistry in 170 formalin-fixed tissue sections representing the entire colorectal adenoma-carcinoma sequence. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to search for FasL mRNA. Analysis of survival was performed in patients with carcinomas. RESULTS: A significant positive linear correlation was found between FasL expression and tumour progression throughout the colorectal adenoma-carcinoma sequence (r(s)=0.677 P<0.001). A pattern of high FasL expression was detected in 19% of high grade adenomas, 40% of stage I-II, 67% of stage III and 70% of stage IV carcinomas. No significant differences were observed between FasL expression in the primary tumours and that in the corresponding liver metastases. The specificity of FasL expression was confirmed at RT-PCR. For stage I-II carcinomas, the 5 year survival was 90% in patients without, or with moderate, tumoural FasL expression compared with 60% in those with high tumoural FasL expression (P<0.05). CONCLUSIONS: Our findings suggest that FasL expression may be involved in the development of colorectal cancer and its progression.

Cell cycle-dependent metabolism of pyrimidine deoxynucleoside triphosphates in CEM cells.

We incorporated 3H-labeled thymidine, deoxycytidine, or cytidine into dNTPs and DNA of exponentially growing CEM cells. G1 and S phase cells were separated by centrifugal elutriation, and the size and specific activity of dNTP pools were determined to study the cell cycle-dependent regulation of specific dNTP synthesizing enzymes in their metabolic context. With [3H]thymidine, we confirm the earlier demonstrated S phase specificity of thymidine kinase. Incorporation of radioactivity from [5-3H]deoxycytidine into dCTP occurred almost exclusively in G1 cells. During S phase, de novo synthesis by ribonucleotide reductase was switched on, resulting in a 70-fold dilution of [3H]dCTP, confirming that ribonucleotide reductase is an S phase-specific enzyme, whereas deoxycytidine kinase is not. [5-3H]Cytidine appeared in dCTP almost to the same extent in G1 as in S phase, despite the S phase specificity of ribonucleotide reductase. During S phase, DNA replication greatly increased the turnover of dCTP, requiring a corresponding increase in ribonucleotide reductase activity. During G1, the enzyme maintained activity to provide dNTPs for DNA repair and mitochondrial DNA synthesis. The poor incorporation of isotope from deoxycytidine into DNA earlier led to the suggestion that the nucleoside is used only for DNA repair (Xu, Y-Z., Peng, H., and Plunkett, W. (1995) J. Biol. Chem. 270, 631-637). The poor phosphorylation of deoxycytidine in S phase provides a better explanation.

Synergistic antiviral action of ribonucleotide reductase inhibitors and 3'-azido-3'-deoxythymidine on HIV type 1 infection in vitro.

Ribonucleotide reductase inhibitors reduce the cellular supply of DNA precursors(dNTP) by interfering with their de novo synthesis. A secondary effect is the stimulation of the uptake and phosphorylation of extracellular deoxynucleosides, including their analogs, e.g., 3'-azidothymidine (AZT). Both effects are relevant to HIV replication, which requires dNTP and is impaired by the triphosphate of AZT. Earlier we demonstrated that ribonucleotide reductase inhibitors--hydroxyurea, and two deoxycytidine analogs specifically active in lymphoid cells--increased the phosphorylation of AZT in CEM cells by prolonging the S phase of the cell cycle. Here we tested the effects of long-term treatments on HIV proliferation in CEM cells and stimulated human lymphocytes infected with HIV-1IIIB. Treatment with low doses of AZT (0.05-0.1 microM) and either hydroxyurea (25-100 microM) or 2'-azido-2'-deoxycytidine (0.25-4 microM) lasted 2 weeks, during which p24 in the culture medium was monitored. Noninfected CEM cells were treated in parallel to measure the inhibition of cell growth, distribution along the cell cycle, dNTP pool size, and level of tritiated AZT phosphorylation. A clear synergism between AZT and ribonucleotide reductase inhibitors was observed at nontoxic doses that induced only minor changes in the cellular parameters measured. The reductase inhibitors by themselves interfered with replication only at doses that inhibited cell proliferation.

Flow cytometric DNA analysis does not predict the radiochemoresponsiveness of esophageal cancer.

The relationship between the DNA pattern and the responsiveness to chemotherapy or chemoradiotherapy has been evaluated in 30 patients with squamous cell carcinoma of the esophagus. In 24 patients polychemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1,000 mg/m2/24 h, continuous infusion of 120 h) every 3 weeks, was performed. Six other patients received chemoradiotherapy with cisplatin 80 mg/m2 on day 1 and 18.5 Gy (split course). Before treatment, at least three endoscopic biopsies were taken from each tumor and frozen at -85 degrees C. Five patients were excluded from the evaluation, three because of interrupted treatment and two due to unsuitable biopsy material obtained endoscopically. The response rate to the cytoreductive treatment was 40% (10/25). DNA content was analyzed with flow cytometry. Out of 25 evaluable patients, a diploid and aneuploid tumor was present in 8 (32.0%) and 17 (68.0%) patients, respectively. According to the DNA pattern, a major response was observed in 4 of 8 patients with a diploid tumor and in 6 of 17 patients with an aneuploid tumor (P = 0.5). No relationship between the percentage of cells in the S-phase and the response to the cytoreductive treatment was evident. Although a slightly higher percentage of major responses was found in euploid tumors, there is no evidence that flow-cytometric DNA analysis can be helpful in the selection of patients for chemotherapy or chemoradiotherapy.

HIV-1 variability and progression to AIDS: a longitudinal study.

HIV-1 replicative activity and its relation to the clinical and immunological evolution of infection was studied in a group of 150 HIV-1 seropositive Italian i.v. drug abusers over a 1 year period. HIV-1 was isolated from 90 (60%) subjects; two groups of isolates were distinguished, according to replicative activity "in vitro" and ability to induce cytopathic effects in cell cultures, and were termed "rapid-high" and "slow-low" viruses, in agreement with other workers. Rapid-high viruses were recovered more frequently from patients with ARC/AIDS, while slow-low viruses seemed related to the asymptomatic period of infection. The replicative properties of HIV-1 seem to affect strongly the course of disease. In fact, an important CD4 cell decline occurred in asymptomatic subjects with rapid-high virus infection; asymptomatic subjects with negative viral cultures or with slow-low viruses showed no such decline. Asymptomatic subjects with negative viral cultures had no signs of disease during the observation period, while 9% with slow-low virus and 45% with rapid-high virus progressed to AIDS.

[Physiopathology of the short bowel: apropos of 2 cases]. / Fisiopatologia do intestino curto: a propósito de dois casos.

A 54 years old white woman and a 38 years old white man with short-bowel disease are reported. Both of them were submitted to surgical procedures for urinary oxalate calculi. They presented malabsorption syndrome with steatorrhea and severe malnutrition. The patients received parenteral nutrition. The woman had also cholelithiasis and acute pancreatitis. The clinical and laboratory data are presented and the pathophysiology of short-bowel disease with emphasis on bile salts depletion, the effect of bile salts on colon oxalate absorption, and intestinal loss of water is commented. The management of short-bowel disease and the use of cholesteramine and the supplementary diet is discussed.

Sister chromatid exchanges and chromosomal aberrations in mouse cells infected with the Abelson and Moloney leukemia viruses.

'Spontaneous' and mitomycin C (MMC)-induced sister chromatid exchanges (SCE) and chromatid breaks were scored in ANN-1 fibroblasts, a non-producer mouse cell line transformed by the Abelson murine leukemia virus (A-MuLV), a replication defective retrovirus whose genome contains the v-abl oncogene. Normal, non-transformed NIH3T3 fibroblasts were used as control. SCE and chromatid break frequencies in untreated or MMC-treated ANN-1 and NIH3T3 cells were compared with those observed in the same cells after infection with the helper murine Moloney leukemia virus (M-MuLV), which rescues the ability of A-MuLV to replicate in ANN-1 cells. The frequency of spontaneous and MMC-induced SCE were not significantly different in both ANN-1 and NIH3T3 cells, independently of M-MuLV infection. After M-MuLV infection, however, increased 'spontaneous' frequency of SCE and altered susceptibility to the induction of SCE by MMC was observed in both cell lines compared to M-MuLV-uninfected cells. In the case of chromatid breaks, the baseline frequency was not significantly different between the two cell lines both in the presence or in the absence of M-MuLV infection, nor was it significantly increased by M-MuLV, with respect to the value observed in uninfected cells. These results indicate that, at variance with what occurs with SCE, viral replication is not needed to increase the frequency of chromosomal aberrations and that the portion of A-MuLV genome alone is sufficient to increase chromatid breaks but not SCE in ANN-1 cells. Thus, in mouse cells carrying retroviruses, SCE and chromosomal aberrations seem to be independently generated, and influenced by different viral genes.

HTLV-III and HTLV-I infection in populations at risk in the Veneto region of Italy.

A seroepidemiological survey has been carried out in the Veneto region to determine the prevalence of HTLV-III and HTLV-I antibodies in subjects at risk for development of AIDS and related conditions. Serum samples were tested by ELISA and, for confirmation, by radioimmunoassay (Western blot), using disrupted virus as antigen. The results show that 22 out of 112 hemophiliacs had antibodies against HTLV-III; however disaggregation of data resulted in 22.6 and 77.8% positivity for patients with severe forms of hemophilia A and B, respectively. Two patients with hemophilia A and two with hemophilia B were positive for antibodies to HTLV-I. The prevalence of HTLV-III antibodies in the homosexual and intravenous drug abuser groups was 52 and 33% respectively. No positive cases for antibodies to HTLV-I were found in homosexuals, while 4.3% seropositivity to HTLV-I was observed in drug abusers. Among patients suffering from various pathologic conditions not strictly AIDS related, only 1 with generalized non-Hodgkin lymphoma was positive for HTLV-I antibodies. In a further group of patients with clinical diagnosis of LAS and AIDS, antibodies to HTLV-III were found in 90 and 100% respectively, while seropositivity for HTLV-I was observed only in 6.4% of LAS patients. The implications of these findings are discussed, particularly in view of the potential oncogenic effect possessed by HTLV-I.