Vascular endothelial growth factor (VEGF) receptor antibody bevacizumab (avastin) induces regression of renal cell carcinoma in an adolescent resulting in residual tumorectomy

Renal cell carcinoma is a chemo- and radiation-resistant malignancy that is very rare in childhood. In advanced cases, survival is extremely poor, but cure can be achieved with complete tumorectomy. We report a 14-year-old female with left renal cell carcinoma, with regional lymphadenopathy extending up to the diaphragm. Complete tumor resection was impossible. The tumor progressed after 10 months of treatment with high-dose interleukin-2. After 7 months of outpatient vascular endothelial growth factor receptor antibody bevacizumab and no significant adverse effects, dramatic tumor shrinkage enabled complete resection.     

The relationship between quality of life and clinical efficacy from a randomized trial comparing olanzapine and ziprasidone

OBJECTIVE: To examine treatment-specific changes in health-related quality of life (QOL) among patients with schizophrenia and to assess the association between clinical and QOL improvement. METHOD: This post hoc analysis used the findings of a 28-week, randomized, multicenter trial of patients with schizophrenia (DSM-IV) treated with olanzapine (10-20 mg/day) or ziprasidone (80-160 mg/day). Data were collected from August 2001 to December 2002. Efficacy was measured using the Positive and Negative Syndrome Scale (PANSS). Quality of life was assessed with the generic health self-administered Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36) and the disease-specific expert-administered Heinrichs-Carpenter Quality of Life Scale (QLS). Mixed-effects-repeated-measures and last-observation-carried-forward approaches were used to assess the effects of treatment on QOL and the association of clinical outcomes to QOL outcomes. RESULTS: Olanzapine- and ziprasidone-treated patients demonstrated similar improvement from baseline to endpoint on the SF-36 and QLS. All correlations between changes in PANSS scores and the SF-36 were significant (p < .001), ranging from -0.159 to -0.400. All correlations between changes in PANSS scores and the QLS were significant (p < .0001), ranging from -0.286 to -0.603. The correlations between the 2 QOL measures were generally significant but small to moderate in magnitude. CONCLUSIONS: The results of this study indicate that, in patients with schizophrenia, olanzapine and ziprasidone treatment are associated with significant QOL and clinical improvements. Further, the significant correlation between change scores on the PANSS and QOL measures suggests that treatment-related clinical improvements are associated with improved health-related and disease-specific QOL. CLINICAL TRIALS REGISTRATION: ClinicalStudyResults.org identifier 2347.     

Oxidative stress in glial cultures: detection by DAF-2 fluorescence used as a tool to measure peroxynitrite rather than nitric oxide

4,5-diaminofluorescein diacetate (DAF-2DA) is widely used as a fluorescent probe to detect endogenously produced nitric oxide (NO). Recent reports that refer to the high sensitivity of DAF-2 toward NO prompted us to test its efficiency and specificity in a mixed murine primary glial culture model, in which the NO-synthesizing enzyme inducible nitric oxide synthase (iNOS) is expressed by stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Cultures were loaded with DAF-2DA and the fluorescence was measured using confocal microscopy. NO production in the cultures was determined using the ozone/chemiluminescence technique. Due to the extremely high photosensitivity of DAF-2, low laser intensities were used to avoid artifacts. No difference in DAF-2 fluorescence was observed in NO-producing cultures compared to control cultures, whereas the NO/peroxynitrite-sensitive dye 2,7-dihydrodichlorofluorescein (DCF) showed a significant fluorescence increase specifically in microglia cells. A detectable gain in fluorescence was seen when NO-containing buffer was added to the DAF-2DA-loaded cells with a minimum NO concentration at 7.7 microM. An additional gain of DAF-2 fluorescence was obtained when the cells were depleted of glutathione (GSH) with L-buthionine S,R-sulfoximine (BSO). Hence, we monitored the change in DAF-2 fluorescence intensity in the presence of NO and O(-*)(2) in a cell-free solution. The fluorescence due to NO was indeed larger when O(-*)(2) was added, implying a higher sensitivity of DAF-2 for peroxynitrite. Nevertheless, our results also indicate that measurement of DCF fluorescence is a better tool for monitoring intracellular changes in the levels of NO and/or peroxynitrite than DAF-2.     

A report on serious pulmonary toxicity associated with gemcitabine-based therapy

Background: Serious pulmonary toxicity(SPT) has recently been noted withgemcitabine-based therapy (G). However,the incidence of SPT has not been fullyevaluated. This retrospective reviewestimates the incidence of, and the factorsinfluencing, SPT with G. Patients and methods: Pulmonarytoxicity was defined as dyspnea,interstitial pneumonitis, lung disorder,lung edema, lung fibrosis, pneumonia,respiratory disorder, and respiratorydistress syndrome. Patients wereidentified from 2 worldwide Lillydatabases – the clinical trial database(CTD) and the safety database (SD). Eventsdesignated as serious and possibly/probablyrelated to therapy by the primary physicianwere independently evaluated and confirmed. Serious pulmonary toxicity events werecategorized as dyspnea or other SPT events. Results: Of the 91 patientsidentified by the investigator in the CTDas having G-related SPT, 32 had G-relatedSPT per the independent reviewers. Basedon the 4448 patients treated with G in theCTD, the incidences of dyspnea and otherSPT events were 0.45% and 0.27%,respectively. Of the 295 patientsidentified by the investigator in the SD ashaving G-related SPT, 167 had G-related SPTper the independent reviewers. Based on anestimated 217,400 patients treated withcommercial G worldwide, the crudeincidences of dyspnea and other SPT eventswere 0.02% and 0.06%, respectively. Conclusions: SPT associated with G isuncommon. Incidences from the CTD fordyspnea and other SPT are 0.45% and0.27%, respectively. Incidences from theSD for dyspnea and other SPT are 0.02% and0.06%, respectively. The influence ofother factors, such as anticancertherapies, on these incidences needs to bebetter understood.     

Endovascular treatment of a ruptured giant serpentine aneurysm of the superior cerebellar artery in a patient with a Chiari II malformation

We present a case of a ruptured giant serpentine aneurysm (GSA) of the superior cerebellar artery in a patient with a Chiari II malformation. The fusiform aneurysm was successfully treated with endovascular parent artery occlusion of the GSA by using detachable coils.     

Multiple sclerosis: comparison of trace apparent diffusion coefficients with MR enhancement pattern of lesions

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging and the trace apparent diffusion coefficient (ADC) provide important structural information about tissues. The purpose of this study was to investigate the relationship between trace ADC values and the enhancement pattern of multiple sclerosis (MS) lesions. METHODS: Ninety-six lesions, identified in 24 patients with MS, were characterized by their enhancement pattern on contrast-enhanced T1-weighted MR images. There were 57 nonenhancing lesions (NELs), 28 homogeneously enhancing lesions (HELs), and 11 ring-enhancing lesions (RELs). The trace ADC means for each type of lesion and for normal-appearing white matter (NAWM) were calculated and compared using Student's t-test. RESULTS: The mean trace ADC values for HELs (mean, 7.7 x 1(-10) m2s(-1); SD, 1.4 x 10(-10) m2s(-1)) were less than those for RELs (mean, 1.2 x 10(-9) m2s(-1); SD, 3.5 x 10(-10)m2s(-1)) and NELs (mean, 1.3 x 10(-9) m2(s-1); SD, 2.6 x 10(-10) m2(s-1)). There was a significant difference between the mean trace ADC values of HELs and RELs as well as between those for HELs and NELs. There was also a significant difference in the mean trace ADC values between all lesion types and NAWM (mean, 6.9 x 10(-10) m2s(-1); SD, 5.0 x 10(-11) m2s(-1)). CONCLUSION: We found a predictable relationship between mean trace ADC and the pattern of enhancement in MS lesions, corresponding to reported histopathologic differences in myelination between lesion types and magnetization transfer ratios.