Measuring quality of life in patients with melanoma: development of the FACT-melanoma subscale

A systematic review of the literature on quality of life (QOL) in melanoma patients suggested an overwhelming need for a disease-specific subscale. A melanoma subscale for the Functional Assessment of Cancer Therapy (FACT-Melanoma) was developed to meet this need. This instrument was developed in three stages. In stage I, the literature was comprehensively reviewed, and over 300 cancer-specific items from the Functional Assessment of Chronic Illness Therapy (FACIT) item bank were examined to identify questions of potential relevance to melanoma patients. In stage II, 20 melanoma experts identified questions that were relevant to melanoma patients and that were to be included in a pilot questionnaire. In stage III, the pilot questionnaire and a semistructured interview to assess item comprehension, relevance, and overall content were administered to 40 patients with various stages of melanoma. In all, 97 items were culled from the literature and the FACIT item bank; after items were reviewed and evaluated, 25 questions were retained. Most patients considered the content of the pilot questionnaire to be relevant (95%), comprehensive (60%), and easy to understand (88%). After final revisions were made, the FACT-Melanoma tool included 24 items encompassing three QOL domains: 20 items relate to physical well-being, 3 to emotional well-being,and 1 to social well-being.The face and content validity of the FACT-Melanoma assessment tool has been confirmed in melanoma patients and by professionals. Formal validation and reliability testing of the questionnaire is being determined in a prospective cohort of melanoma patients.     

General population and cancer patient norms for the Functional Assessment of Cancer Therapy-General (FACT-G)

Given the number of new cancer cases diagnosed each year and the increases in survival rates, the importance of having a clinically useful health-related quality of life (HRQOL) instrument has increased. The Functional Assessment of Cancer Therapy-General (FACT-G) is one such instrument that has been used worldwide to assess HRQOL. Previously, the use of the FACT-G had been limited because of a lack of published normative data. Normative data are useful for consumers to place their results in an appropriate context by comparing their scores of individuals or group of individuals to a reference group. Here, we present normative data for the FACT-G for two reference groups: (a) a sample of the general U.S. adult population and (b) a large, heterogeneous sample of adult patients with cancer. In addition, we demonstrate various uses of the normative data.     

Development of the Childhood Atopic Dermatitis Impact Scale: initial validation of a quality-of-life measure for young children with atopic dermatitis and their families

To measure the effects of atopic dermatitis (AD) on the quality of life of affected young children and their families, we developed a prototype 62-item instrument, the Childhood Atopic Dermatitis Impact Scale (CADIS). The prototype CADIS was developed from a comprehensive conceptual framework based on data from parents and clinicians. The instrument had eight subscales (four each for child and parent): physical health, emotional health, physical functioning, and social functioning. The goal of this work was to test the validity of and to refine the prototype of CADIS. Two hundred seventy parents of children under the age of 6 y with AD responded to the instrument. Content validity was demonstrated by expert and parent reviews of the drafted and refined instrument, and by analyzing parents' responses to open-ended questions about their children's skin disease. Construct validity was assessed in exploratory factor analyses which supported a refinement in the conceptual framework to consist of two dimensions with five domains: child dimensions (symptoms and activity limitation/behavior), and parent dimensions (family/social function, sleep, and emotions). Seventeen items were eliminated, yielding a 45-item refined version of CADIS (score 0-180) with evidence of content and construct validity and suggested use in clinical research.     

Ultrasound biomicroscopy findings in peripheral vitreoretinal toxocariasis

PURPOSE: To describe the morphologic alterations in ultrasound biomicroscopy (UBM) present in peripheral vitreoretinal toxocariasis. METHODS: An observational prospective study of case series. Fifteen eyes of 15 patients with clinical and laboratory diagnosis of peripheral vitreoretinal toxocariasis were enrolled. The patients were submitted to UBM examination of the region corresponding to the pars plana of the affected eye. RESULTS: The most common morphologic alterations found by UBM in patients with peripheral vitreoretinal toxocariasis were as follows: vitreal membranes (13 cases), toxocara granuloma (11 cases), and pseudocysts (8 cases). Other less frequent findings were thickening of the ciliary body (6 cases), cystic formation (2 cases), peripheral retinal detachment (2 cases), rectification of the iris root (1 case), and posterior synechiae (1 case). CONCLUSIONS: UBM allows detection of well-defined morphologic alterations associated with peripheral vitreoretinal toxocariasis, being useful to reinforce the clinical diagnosis.     

Effects of aminoguanidine and cyclooxygenase inhibitors on nitric oxide and prostaglandin production, and nitric oxide synthase and cyclooxygenase expression induced by lipopolysaccharide in the estrogenized rat uterus

BACKGROUND/OBJECTIVE: The aim of our study was first to investigate if there exists an interaction between nitric oxide (NO) and prostaglandin (PG) generation in the estrogenized rat uterus challenged by lipopolysaccharide (LPS), and, secondly, which isoforms of nitric oxide synthase (NOS) and cyclooxygenase (COX) participate in this process. METHODS: To study the effect of LPS and to characterize the isoenzymes involved in the process, specific inhibitors of iNOS (aminoguanidine) and COX-II (meloxicam, nimesulide) and non-specific of COX (indomethacin) were injected intraperitoneally to determine their effect on NO and PG production, and on NOS and COX expression induced by LPS in estrogenized rat uterus. NO production was measured by arginine-citrulline conversion assay and PGE(2)/PGF(2alpha,)by radioconversion. Enzyme expression was evaluated by Western blot analysis. RESULTS: The present work shows that iNOS inhibitor, aminoguanidine, reduced NO and PGE(2)/PGF(2alpha) production induced by LPS injection. Aminoguanidine exerts its effect over the PG metabolism by inhibiting COX-II activity and expression. On the other hand, both indomethacin, a non-selective PG inhibitor, and meloxicam, a COX-II inhibitor, stimulated NO production and reduced PGE(2)/PGF(2alpha) generation. Indomethacin also reduced COX-II and iNOS expression. CONCLUSION: These results indicate that in the estrogenized rat uterus challenged with LPS, PG and NO interact affecting each other's metabolic pathways. The above findings indicate that the interaction between NOS and COX might be important in the regulation of physiopathologic events during pregnancy.     

IL-10 inhibits nitric oxide synthesis in murine uterus

OBJECTIVES: Recent reports point to a role for the nitric oxide/nitric oxide synthase (NO/NOS) system in implantation. It has been suggested that inducible NOS expressed at peri-implantation would lead to enhanced NO production, which could promote the attachment of the blastocyst. Short-term administration of NO donors during the pre-implantation period reduced the pregnancy rate in a dose-dependent manner. Thus, it is thought that optimal levels of NO are critical for embryo implantation, so regulation of NOS must be crucial. Taking this into consideration, interleukin-10 (IL-10), synthesized and secreted by the embryo, could be modulating NOS during implantation. In this study we have investigated the in vitro effect of IL-10 on NOS in the uterus. METHODS: To determine the effect of IL-10, slices of uterus from estrogenized mice were pre-incubated for 60 min with different concentrations of IL-10 and NOS activity was measured. RESULTS: IL-10 (50 and 100 ng/ml in vitro) diminished NOS activity. The in vivo administration of lipopolysaccharide (LPS; 8 mg/kg) significantly increased the conversion of arginine into citrulline. This effect was abolished after 60 min of preincubation with IL-10 (100 ng/ml). The stimulatory effect of LPS and estrogen on NOS activity is exerted on the Ca-independent isoform and IL-10 in vitro abolished this increase. We observed that the uterus of pregnant mice on day 5 of gestation synthesized NO. This production was significantly inhibited by preincubation with IL-10 (100 ng/ml). CONCLUSIONS: This report demonstrates that IL-10 is capable of inhibiting NO synthesis in estrogenized, LPS-treated and pregnant rat uterus.     

A combination of distribution- and anchor-based approaches determined minimally important differences (MIDs) for four endpoints in a breast cancer scale

OBJECTIVE: To determine distribution- and anchor-based minimal important difference (MID) estimates for four scores from the Functional Assessment of Cancer Therapy-Breast (FACT-B): the breast cancer subscale (BCS), Trial Outcome Index (TOI), FACT-G (the general version), and FACT-B. STUDY DESIGN AND SETTING: We used data from a Phase III clinical trial in metastatic breast cancer (ECOG study 1193; n=739) and a prospective observational study of pain in metastatic breast cancer (n=129). One third and one half of the standard deviation and 1 standard error of measurement were used as distribution-based criteria. Clinical indicators used to determine anchor-based differences included ECOG performance status, current pain, and response to treatment. RESULTS: FACT-B scores were responsive to performance status and pain anchors, but not to treatment response. By combining the results of distribution- and anchor-based methods, MID estimates were obtained: BCS=2-3 points, TOI=5-6 points, FACT-G=5-6 points, and FACT-B=7-8 points. CONCLUSION: Distribution- and anchor-based estimates of the MID do show convergence. These estimates can be used in combination with other measures of efficacy to determine meaningful benefit and provide a basis for sample size estimation in clinical trials.     

Markers of endothelial function in pediatric stem cell transplantation for acute leukemia

BACKGROUND: Endothelial cells and leukocytes intimately interact in inflammation and coagulation processes, so that dysregulation of their function may lead to both cellular damage and thrombosis, which may occur as complications of bone marrow transplantation (BMT). Partially conflicting evidence about endothelial markers and their relationships with clinical complications after BMT has been reported in the literature. Since almost all studies were carried out in adults, we evaluated some recent available markers of endothelial cell function in pediatric patients undergoing stem cell transplantation (SCT) for acute leukemia. PROCEDURE: We studied the variation in circulating serum endothelial-selectin (ES), leukocyte-selectin (LS), thrombomodulin (TM), von Willebrand factor (vWF), nitrate + nitrite (NO(2) (-)/NO(3) (-)), endothelin-1 (EN), and tissue factor (TF) in 21 pediatric patients undergoing SCT for acute leukemia. RESULTS: ES and LS significantly lowered following SCT and returned to pre-SCT levels 4 weeks after the procedure. NO(2) (-)/NO(3) (-) markedly increased following SCT. Also, TM and vWF increased, although such changes did not reach statistical significance. EN and TF did not appreciably change. A strong correlation was observed between white blood cell (WBC) count and both ES and LS, as well as between such selectins. TM significantly correlated with both selectins and NO(2) (-)/NO(3) (-). The pre-conditioning levels of TM and vWF in patients undergoing major complications, considered altogether, were significantly lower and higher, respectively, than in uncomplicated patients. NO(2) (-)/NO(3) (-) levels 3 and 4 weeks post-SCT were significantly lower in patients suffering from veno occlusive disease. Both selectins were significantly higher in allo- than in auto-transplanted patients 4 weeks after SCT. CONCLUSIONS: Our data support the hypothesis of severe endothelial damage after conditioning and SCT, particularly allogeneic. However, the increase in TM, which has strong anticoagulant properties, and metabolites of NO, involved also in protective actions, may reflect regeneration of the anti-thrombotic endothelial function. This could take place after transitory functional impairment, rather than pure endothelial damage.     

The GABAB receptor and recognition memory: possible modulation of its behavioral effects by the nitrergic system

Functional activation of the GABA(B) receptor inhibits learning and memory processes, though discrepant findings, in this context, have also been reported. The present study was designed to investigate the role of the GABA(B) receptor on recognition memory in the rat. For this purpose, the effects induced by the GABA(B) agonist baclofen and the GABA(B) antagonist P-(3-aminopropyl)-P-diethoxymethylphosphinic acid (CGP 35348) on memory were assessed by using the object-recognition task. In addition, the possible involvement of the nitrergic system on GABA(B) receptor's effects was also evaluated by using the same behavioral procedure. This is a working-memory paradigm based on the differential exploration of a new and familiar object. In a first dose-response study, baclofen (0.5, 2, and 4 mg/kg, i.p.), dose-dependently impaired animals' performance in this task, suggesting a modulation of acquisition and storage of information. CGP 35348 (100 and 300 mg/kg, i.p.), counteracted these baclofen-induced performance deficits. The nitric oxide donor molsidomine, at the dose of 4 but not 2 mg/kg, i.p, successfully antagonized the deficits on cognition induced by the highest dose of baclofen (4 mg/kg). These results indicate a) that the GABA(B) receptor is involved in recognition memory and b) that an NO component modulates the effects of the GABA(B) receptor on learning and memory.