Topical diclofenac in 2.5% hyaluronan inhibits basal cell carcinoma, actinic keratosis, and murine colon-26 growth in vivo. colon-26 tumor growth was preceded by angiogenesis and reduced apoptotic ...and mitotic indices. Diclofenac reduced proliferation and viability in vitro, and stimulated apoptosis. Hyaluronan inhibited proliferation and viability at 1 mg/ml but was inactive below this level. Topical application of diclofenac inhibited tumor prostaglandin synthesis and retarded angiogenesis and tumor growth (ratio of treatment:control, 0.174). The mitotic index remained unaltered in vivo, whereas the apoptotic index and necrosis were increased. Topical vehicle exhibited slight antitumor and antiangiogenesis activity. The substantial quantities of diclofenac delivered locally in hyaluronan may exhibit antitumor activity in similar fashion to those seen in vitro and explain its clinical efficacy.
Background. In a previous study we showed that within a budget constraint, most people would rather offer a less effective screening test to 100% of a Medicaid population, thereby saving 1,000 lives, ...than a more effective test to 50% of the population, thereby saving 1,100 lives. We present here a study exploring whether this preference for equity over efficiency persists when neither test can be offered to the entire population. Methods. Members of Physicians' Online and prospective jurors at the Philadelphia County Courthouse randomly received 1 of 3 questionnaires (Q1, Q2, or Q3) describing a limited budget to screen Medicaid enrollees for colon cancer. In all questionnaires, test 1 was said to save 1,000 lives, and test 2, a more effective and more expensive test, was said to save 1,100. In Q1, test 1 was offered to 100% and test 2 to 50% of the population. In Q2, the 2 tests could be offered to 50% and 25%, respectively; in Q3, to 90% and 40%, respectively. Respondents indicated which test they recommended and provided justification. Results. The majority of physicians (59%) and the general public (56%) receiving Q1 favored the less effective screening test. However, of those receiving Q2, only 26% of physicians and 27% of the general public recommended the less effective screening test. And of those receiving Q3, only 38% of physicians and 28% of the general public recommended the less effective test. Justifications for these recommendations were based largely on concerns for equality of treatment among those who chose the less effective test and concerns for saving the most lives among those who preferred the more effective test. Conclusions. Although most respondents show a preference for equity over efficiency when equity means that 100% of a population can receive a service, many fewer respondents maintain this preference when equity is no longer absolute. This result suggests that the preference for equity is sometimes "all or none."
Despite improvements in outcomes after completion of the Fontan circulation, long-term functional state varies. We sought to identify pre- and postoperative characteristics associated with overall ...function.
We analyzed data from 476 survivors with the Fontan circulation enrolled in the Pediatric Heart Network Fontan Cross-sectional Study. Mean age at creation of the Fontan circulation was 3.4 plus or minus 2.1 years, with a range from 0.7 to 17.5 years, and time since completion was 8.7 plus or minus 3.4 years, the range being from 1.1 to 17.3 years. We calculated a functional score for the survivors by averaging the percentile ranks of ventricular ejection fraction, maximal consumption of oxygen, the physical summary score for the Child Health Questionnaire, and a function of brain natriuretic peptide. The mean calculated score was 49.5 plus or minus 17.3, with a range from 3 to 87. After adjustment for time since completion of the circulation, we found that a lower score, and hence worse functional state, was associated with: right ventricular morphology (p less than 0.001), higher ventricular end-diastolic pressure (p equals 0.003) and lower saturations of oxygen (p equals 0.047) prior to completion of the Fontan circulation, lower income for the caregiver (p equals 0.003), and, in subjects without a prior superior cavopulmonary anastomosis, arrhythmias after completion of the circulation (p equals 0.003). The model explained almost one-fifth (18%) of the variation in the calculated scores. The score was not associated with surgical centre, sex, age, weight, fenestration, or the period of stay in hospital after completion of the Fontan circuit. A validation model, using 71 subjects randomly excluded from initial analysis, weakly correlated (R equals 0.17, p equals 0.16) with the score calculated from the dataset.
Right ventricular morphology, higher ventricular end-diastolic pressure and lower saturations of oxygen prior to completion of the Fontan circuit, lower income for the provider of care, and arrhythmias after creation of the circuit, are all associated with a worse functional state. Unmeasured factors also influence outcomes.
Burkitt's lymphoma (BL) is a particularly aggressive cancer that primarily affects African children. Unfortunately, effective and affordable treatment is out of reach of most of the afflicted. The ...illicit psychoactive drug methylenedioxymethamphetamine (MDMA, 'ecstasy') is cytotoxic to BL cell lines, but its low potency, psychoactivity and neurotoxicity preclude consideration as a therapeutic drug candidate. This paper describes the discovery of novel a-aryl analogues of MDMA that lack psychoactivity and reduce BL cell line viability with significantly more potency than the lead compound. Preliminary in vitro studies also indicate that the compounds are non-toxic to a relevant neuronal cell line.
Health is a key component of human development, growth and quality of life. The Health, Medicine and Human Development book series aim to provide a public forum for book publications from a ...multidisciplinary group of researchers, practitioners and clinicians for an international professional forum interested in the broad spectrum of health, medicine and human development. We welcome research on a wide variety of substantive areas that will promote and impact healthy human development including prevention, intervention and care also among people in vulnerable conditions.
Diclofenac in hyaluronan is analgesic and angiostatic. The depletion of substance P may be a common mechanism. Mice received diclofenac, diclofenac in hyaluronan, or saline i.v. for 5 days and snout ...substance P assessed: saline 2.80±0.23; 0.5 mg/kg diclofenac 2.03±0.20 (
P<0.05); diclofenac in hyaluronan 1.88±0.21 (
P<0.02); capsaicin 1.45±0.26 fmol/mg tissue (
P<0.005). Substance P recovered by 5 days (diclofenac in hyaluronan, capsaicin) and 24 h (diclofenac). Diclofenac may deplete substance P in analgesia, and hyaluronan prolong the depletion.
Cytogenetic and DNA flow cytometric analyses of leukemic cells from 1.971 children with newly diagnosed acute lymphoblastic leukemia (ALL) identified stem lines with modal chromosome numbers greater ...than 65 in 26 patients (1.3%). Near-triploidy (66 to 73 chromosomes) was found in six cases and near-tetraploidy (82 to 94 chromosomes) in 20. A striking morphologic finding was the presence of clumped chromatin with grooved nuclei or Rieder cell formation in 20 cases. Other than a slight excess of the pre-B immunophenotype, the near-triploid cases did not appear to differ substantially from the general ALL population in clinical features. In contrast, near-tetraploid cases were more often associated with a T-cell immunopheno-type (47% v 14%, P< .001) and L2 morphology (30% v 22%, P < .01), and were older at diagnosis (median age, 8.6 v 4.8 years, P = .01) than cases with other ploidies. Moreover, an unusually high proportion of near-tetraploid cases tested (6 of 15) expressed one or more of the myeloid-associated antigens CD13, CD15, and CD33. Despite the use of contemporary intensive chemotherapy and short follow-up for most patients, 6 of the 20 near-tetraploid cases have relapsed or died. This study suggests that the near-tetraploid subtype differs from other cases of hyperdiploid >50 ALL, which have been associated with a favorable prognosis.
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