Enhancement of gemcitabine cytotoxicity in pancreatic adenocarcinoma through controlled release of nitric oxide.

Gemcitabine (GEM) is the first-line treatment for pancreatic adenocarcinoma (PAC) yet chemoresistance is common. Nitric oxide (NO) is the predominant species responsible for the cytotoxic action of macrophages against cancer cells yet localized delivery is difficult given the short half-life. We sought to study the effect of locally delivered NO on GEM mediated PAC cytotoxicity and the potential role of SMAD4 in this effect. We hypothesized that NO would enhance the cytotoxicity of GEM in a SMAD4 dependent manner. NO-Silica nanoparticles (NO-Si) were synthesized via a co-condensation of tetraethoxysilane with aminoalkoxysilane under high-pressure nitrous oxide. NO release was measured using chemiluminescence. A SMAD4 negative PAC cell line (SMAD4-) was made using retroviral knockdown of Panc1 PAC cells. Panc1 and SMAD4- cells were treated with gemcitabine (100 nm (hi) to 30 µm (lo)), 30 mg NOSi particles, or both (NOSihi or NOSilo) and cell viability assessed. NoSi reduced cell viability by 25.99% in Panc1 and 24.38% in SMAD4-. When combined with gemcitabine, further reductions were seen in a dose dependent manner for both cell lines. We have demonstrated the in-vitro dose dependent cytotoxic effects of NOSi. When combined with GEM there is a synergistic effect resulting in improved cytotoxicity seen in both Panc1 and SMAD4- PAC cells with a differential pattern of cell death seen at high concentrations of NO. These findings suggest not only that NO is useful chemosensitizing agent but that SMAD4- may play a role in its synergism with GEM.

Workload Indicators of Staffing Need method in determining optimal staffing levels at Moi Teaching and Referral Hospital.

BACKGROUND: There is an increasing demand for quality healthcare in the face of limited resources. With the health personnel consuming up to three quarters of recurrent budgets, a need arises to ascertain that a workforce for any health facility is the optimal level needed to produce the desired product. OBJECTIVE: To highlight the experience and findings of an attempt at establishing the optimal staffing levels for a tertiary health institution using the Workload Indicators of Staffing Need (WISN) method popularised by the World Health Organisation (WHO), Geneva, Switzerland. DESIGN: A descriptive study that captures the activities of a taskforce appointed to establish optimal staffing levels. SETTING: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya, a tertiary hospital in the Rift Valley province of Kenya from September 2005 to May 2006. MAIN OUTCOME MEASURES: The cadres of workers, working schedules, main activities, time taken to accomplish the activities, available working hours, category and individual allowances, annual workloads from the previous year's statistics and optimal departmental establishment of workers. RESULTS: There was initial resentment to the exercise because of the notion that it was aimed at retrenching workers. The team was given autonomy by the hospital management to objectively establish the optimal staffing levels. Very few departments were optimally established with the majority either under or over staffed. There were intradepartmental discrepancies in optimal levels of cadres even though many of them had the right number of total workforce. CONCLUSION: The WISN method is a very objective way of establishing staffing levels but requires a dedicated team with adequate expertise to make the raw data meaningful for calculations.