Effect of de novo purine synthesis inhibitors on 5-fluorouracil metabolism and cytotoxicity

Methotrexate pretreatment of L1210 cells had been shown previously by us to cause an enhancement of the intracellular accumulation of 5-fluorouracil and of the formation of 5-fluorouracil nucleotides which was correlated with synergistic cytotoxicity. This effect of methotrexate was associated with increases in 5-phosphoribosyl-1-pyrophosphate, the cofactor required for the conversion of 5-fluorouracil to 5-fluorouridine-5'-monophosphate (FUMP). Because these influences on 5-fluorouracil metabolism were most likely mediated by the activity of methotrexate as an inhibitor of purine synthesis, the effects of other agents that inhibit purine synthesis were examined. An inhibitor of amidophosphoribosyltransferase, 6-methylmercaptopurine ribonucleoside, the glutamine antagonists, azaserine and 6-diazo-5-oxo-L-norleucine (DON), and the L-aspartate analogue inhibitor of adenylsuccinate synthetase, L-alanosine, all reduced the incorporation of [1-14C]glycine into adenine and guanine bases isolated from nucleic acids. Each drug also resulted in intracellular elevations of 5-phosphoribosyl-1-pyrophosphate that were 15- to 25-fold greater than control levels. These alterations in de novo purine nucleotide synthesis were associated with enhanced intracellular 5-fluorouracil accumulation and synergistic cytotoxicity.     

Cell‐assisted lipotransfer: Friend or foe in fat grafting? Systematic review and meta‐analysis

Autologous fat grafting is a common procedure for soft‐tissue reconstruction but is associated with a graft resorption rate ranging from 20% to 80%. To improve the fat graft survival rate, a new technique, called cell‐assisted lipotransfer (CAL), was developed. With CAL, fat is injected along with adipose‐derived stromal cells that are assumed to improve fat survival rate. We conducted an evidence‐based meta‐analysis to evaluate the efficacy and safety of CAL as compared with conventional autologous fat grafting (non‐CAL). The databases MEDLINE (via PubMed), Cochrane Library, EBSCO, Web of Science, and EMBASE were searched for reports of clinical trials, case series, and cohorts available from 2008 to 2016. We conducted a meta‐analysis of the efficacy of CAL with data analysis concerning fat survival rate. The incidence of complications and the need for multiple procedures were evaluated to determine the safety of CAL. We identified 25 studies (696 patients) that were included in the systematic review; 16 studies were included in the meta‐analysis to evaluate the efficacy of CAL. The fat survival rate was significantly higher with CAL than non‐CAL (64% vs. 44%, p < .0001) independent of injection site (breast and face). This benefit of CAL was significant for only injection volumes <100 ml (p = .03). The two groups did not differ in frequency of multiple procedures after fat grafting, but the incidence of complications was greater with CAL than non‐CAL (8.4% vs. 1.5%, p = .0019). The CAL method is associated with better fat survival rate than with conventional fat grafting but only for small volumes of fat grafting (<100 ml). Nonetheless, the new technique is associated with more complications and did not reduce the number of surgical procedures needed after the first fat grafting. More prospective studies are required to draw clinical conclusions and to demonstrate the real benefit of CAL as compared with common autologous fat grafting.     

Hyperphosphatemia and hypocalcemia accompanying rapid cell lysis in a patient with Burkitt's lymphoma and Burkitt cell leukemia

Hyperphosphatemia, hypocalcemia and acute oliguric renal failure resulting from uric acid nephropathy developed in a patient with Burkitt's lymphoma and Burkitt cell leukemia after effective chemotherapy. A review of other reported cases in which the patients had similar metabolic abnormalities is presented, and the pathophysiology is discussed. The clinical setting in which these metabolic developments are most likely to occur is defined, and an approach for their prevention and management is presented.     

Brief report: evaluating the Bedtime Pass Program for child resistance to bedtime--a randomized, controlled trial

OBJECTIVE: To evaluate the Bedtime Pass Program (BPP), an extinction-based procedure for treating bedtime resistance in typically developing children. METHODS: A randomized, controlled trial in which nineteen 3- to 6-year-old children demonstrating bedtime resistance were randomly assigned to a Bedtime Pass or Monitoring Control group. The experimental condition involved parent monitoring plus the Bedtime Pass: a card exchangeable for one parental visit or excused departure from the room after bedtime, with parents ignoring subsequent bids for attention. RESULTS: Children in the Bedtime Pass condition left their rooms and called and cried out significantly less frequently than controls. They demonstrated significant reductions in the time required to quiet each night. Treatment effects were maintained at 3-month follow-up. Parents reported high levels of satisfaction and treatment acceptability. CONCLUSIONS: BPP is a noncomplex, socially acceptable, effective treatment for bedtime resistance. It retains the powerful effects of extinction-based procedures without the "extinction burst."     

African media coverage of tobacco industry corporate social responsibility initiatives

Guidelines for implementing the World Health Organization's Framework Convention on Tobacco Control (FCTC) recommend prohibiting tobacco industry corporate social responsibility (CSR) initiatives, but few African countries have done so. We examined African media coverage of tobacco industry CSR initiatives to understand whether and how such initiatives were presented to the public and policymakers. We searched two online media databases (Lexis Nexis and Access World News) for all news items published from 1998 to 2013, coding retrieved items through a collaborative, iterative process. We analysed the volume, type, provenance, slant and content of coverage, including the presence of tobacco control or tobacco interest themes. We found 288 news items; most were news stories published in print newspapers. The majority of news stories relied solely on tobacco industry representatives as news sources, and portrayed tobacco industry CSR positively. When public health voices and tobacco control themes were included, news items were less likely to have a positive slant. This suggests that there is a foundation on which to build media advocacy efforts. Drawing links between implementing the FCTC and prohibiting or curtailing tobacco industry CSR programmes may result in more public dialogue in the media about the negative impacts of tobacco company CSR initiatives.