Sequence-dependent effects of ZD1839 (‘Iressa’) in combination with cytotoxic treatment in human head and neck cancer

Elevated levels of epidermal growth factor receptor in head and neck cancer have been extensively reported, and are correlated with poor prognosis. The combination of cisplatin and 5-fluorouracil is a standard treatment regimen for head and neck cancer, with radiation representing another therapeutic option. Six head and neck cancer cell lines were used to study the cytotoxic effects of combining ZD1839 (‘Iressa’), a new selective epidermal growth factor receptor tyrosine kinase inhibitor, and radiation. Two of the cell lines were also used to study the combination of ZD1839 and cisplatin/5-fluorouracil. Cytotoxic effects were assessed by the MTT test. The results indicated that ZD1839 applied before radiation gave the best effects (P=0.002); an effect that was strongest in those p53-mutated cell lines that express the highest epidermal growth factor receptor levels. The effects of ZD1839 with cisplatin and/or 5-fluorouracil were sequence dependent (P<0.003), with the best results achieved when ZD1839 was applied first. For the triple combinations, ZD1839 applied before cisplatin and 5-fluorouracil resulted in a slight synergistic effect (P=0.03), although the effect was greater when ZD1839 was applied both before and during cytotoxic drug exposure. In conclusion, ZD1839 applied before radiation and before and/or during cisplatin/5-fluorouracil may improve the efficacy of treatment for head and neck cancer

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Comment: Towards a Viable Local Government Structure in Nigeria: Overview of US and German Local Government Systems

Local governments are principally established for development at the grassroots and they must be structured in a manner that makes them viable and capable of achieving this purpose. The objective of this comment is to appraise the current local government structure under the Nigerian constitutional framework with a view to evolving a more viable structure that will lead to better service delivery at the local level. Comparative reference is made to the local government systems in the United States of America (USA) and Germany so that good practices can be compared with the Nigerian System. The comment suggests a system that will be in tune with the Nigerian local milieu.Key terms: Local government, local administration, one-tier model, two-tier model, hybrid structure, Nigeri

Long-term dominance of Mycobacterium tuberculosis Uganda family in peri-urban Kampala-Uganda is not associated with cavitary disease

Previous studies have shown that Mycobacterium tuberculosis (MTB) Uganda family, a sub-lineage of the MTB Lineage 4, is the main cause of tuberculosis (TB) in Uganda. Using a well characterized patient population, this study sought to determine whether there are clinical and patient characteristics associated with the success of the MTB Uganda family in Kampala.; A total of 1,746 MTB clinical isolates collected from1992-2009 in a household contact study were genotyped. Genotyping was performed using Single Nucleotide Polymorphic (SNP) markers specific for the MTB Uganda family, other Lineage 4 strains, and Lineage 3, respectively. Out of 1,746 isolates, 1,213 were from patients with detailed clinical data. These data were used to seek associations between MTB lineage/sub-lineage and patient phenotypes.; Three MTB lineages were found to dominate the MTB population in Kampala during the last two decades. Overall, MTB Uganda accounted for 63% (1,092/1,746) of all cases, followed by other Lineage 4 strains accounting for 22% (394/1,746), and Lineage 3 for 11% (187/1,746) of cases, respectively. Seventy-three (4 %) strains remained unclassified. Our longitudinal data showed that MTB Uganda family occurred at the highest frequency during the whole study period, followed by other Lineage 4 strains and Lineage 3. To explore whether the long-term success of MTB Uganda family was due to increased virulence, we used cavitary disease as a proxy, as this form of TB is the most transmissible. Multivariate analysis revealed that even though cavitary disease was associated with known risk factors such as smoking (adjusted odds ratio (aOR) 4.8, 95% confidence interval (CI) 3.33-6.84) and low income (aOR 2.1, 95% CI 1.47-3.01), no association was found between MTB lineage and cavitary TB.; The MTB Uganda family has been dominating in Kampala for the last 18 years, but this long-term success is not due to increased virulence as defined by cavitary disease

Where to From Here? The Mechanisms Enabling the Movement of First Instar Caterpillars on Whole Plants Using Helicoverpa armigera (Hübner)

Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) is an economically-important, polyphagous herbivore in Old World countries. The distribution of larvae within various host plants has been described, but few studies have tried to determine the behavioural mechanisms by which the given distributions arose. Our aim was to determine the mechanisms which enable larval movement on pea plants, starting with first instars. Observations and bioassays determined larval movement in response to light and angled surfaces, as well as the effect of feeding and plant volatiles on these responses. The majority (68-72%) of 1st instars were positively phototactic towards blue, green and white light and 42% towards UV light. In the dark, larvae showed negative geotaxis. The angle of their substrate also had a kinetic effect on larvae; the steeper the angle from horizontal the more larvae moved under all conditions. Phenylacetaldehyde (a flower volatile) suppressed larval movement except at 90. (Z)-3-Hexenyl acetate (a green leaf volatile) reversed the direction of movement at the flattest angle. Feeding lessened the probability of moving. We suggest that phototaxis and geotaxis are behaviours common to larval lepidopterans (caterpillars), and that these basic behaviours are modulated by environmental, larval, and plant factors to give observed distributions. Using a multinomial model approach, we created a flow chart to qualitatively and quantitatively represent the decision-making process of first instar H. armigera in response to the factors influencing movement