Drugs for migraine

26.1 Migraine 26.2 Pathogenesis of Migraine 26.3 Cortical Spreading Depression 26.4 Neurogenic Inflammation Theory 26.5 Role of 5-HT in Migraine 26.6 Acute and Prophylactic Treatment of Migraine

Drugs in pregnancy and labour

27. Drugs in pregnancy and labour 27.1 Introduction 27.2 Common complaints in pregnancy and labour and their treatments 27.2.1 Pre-eclampsia and eclampsia. 27.2.2 Suppression of early labour 27.2.3 Neonatal respiratory distress syndrome 27.2.4 Postpartum haemorrhage 27.2.5 Prolactin excess 27.2.6 Nausea

Comparison of cervical and blood T-cell responses to human papillomavirus-16 in women with human papillomavirus-associated cervical intraepithelial neoplasia

Human papillomaviruses (HPVs) are obligate epithelial pathogens and typically cause localized mucosal infections. We therefore hypothesized that T-cell responses to HPV antigens would be greater at sites of pathology than in the blood. Focusing on HPV-16 because of its association with cervical cancer, the magnitude of HPV-specific T-cell responses at the cervix was compared with those in the peripheral blood by intracellular cytokine staining following direct ex vivo stimulation with both virus-like particles assembled from the major capsid protein L1, and the major HPV oncoprotein, E7. We show that both CD4 + and CD8 + T cells from the cervix responded to the HPV-16 antigens and that interferon-γ (IFN-γ) production was HPV type-specific. Comparing HPV-specific T-cell IFN-γ responses at the cervix with those in the blood, we found that while CD4 + and CD8 + T-cell responses to L1 were significantly correlated between compartments (P = 0.02 and P = 0.05, respectively), IFN-γ responses in both T-cell subsets were significantly greater in magnitude at the cervix than in peripheral blood (P = 0.02 and P = 0.003, respectively). In contrast, both CD4 + and CD8 + T-cell IFN-γ responses to E7 were of similar magnitude in both compartments and CD8 + responses were significantly correlated between these distinct immunological compartments (P = 0.04). We therefore show that inflammatory T-cell responses against L1 (but not E7) demonstrate clear compartmental bias and the magnitude of these responses do reflect local viral replication but that correlation of HPV-specific responses between compartments indicates their linkage.

Safety impacts of alcohol and other drugs in construction : development of an industry policy and cultural change management program

There is increasing concern about the impact of employees‟ alcohol and other drug (AOD) consumption on workplace safety and performance, particularly within the construction industry. While most Australian jurisdictions have identified this as a critical safety issue, information is limited regarding the prevalence of AODs in the workplace and there is limited evidential guidance regarding how to effectively and efficiently address such an issue. The current research aims to scientifically evaluate the use of AODs within the Australian construction industry in order to reduce the potential resulting safety and performance impacts and engender a cultural change in the workforce - to render it unacceptable to arrive at a construction workplace with impaired judgement from AODs. The study will adopt qualitative and quantitative methods to firstly evaluate the extent of general AOD use in the industry. Secondly, the development of an appropriate industry policy will adopt a non-punitive and rehabilitative approach developed in consultation with employers and employees across the infrastructure and building sectors, with the aim it be adopted nationally for adoption at the construction workplace. Finally, an industry specific cultural change management program and implementation plan will be developed through a nationally collaborative approach. Final results indicate that a proportion of those sampled in the construction sector may be at risk of hazardous alcohol consumption. A total of 286 respondents (58%) scored above the cut-off cumulative score for risky or hazardous alcohol. Other drug use was also identified as a major issue. Results support the need for evidence-based, preventative educational initiatives that are tailored to the industry. This paper will discuss the final survey and interview results.

Factors affecting technical efficiency of rice farmers in village reservoir irrigation systems of Sri Lanka

Given the importance of water for rice production, this study examines the factors affecting the technical efficiency (TE) of irrigated rice farmers in village irrigation systems (VIS) in Sri Lanka. Primary data were collected from 460 rice farmers in the Kurunagala District, Sri Lanka, to estimate a stochastic translog production frontier for rice production. The mean TE of rice farming in village irrigation was found to be 0.72, although 63% of rice farmers exceeded this average. The most influential factors of TE are membership of Farmer Organisations (FOs) and the participatory rate in collective actions organised by FOs. The results suggest that enhancement of co-operative arrangements of farmers by strengthening the membership of FOs is considered important for increasing TE in rice farming in VIS.

Bioreactor for blood product production

The feasibility of ex vivo blood production is limited by both biological and engineering challenges. From an engineering perspective, these challenges include the significant volumes required to generate even a single unit of a blood product, as well as the correspondingly high protein consumption required for such large volume cultures. Membrane bioreactors, such as hollow fiber bioreactors (HFBRs), enable cell densities approximately 100-fold greater than traditional culture systems and therefore may enable a significant reduction in culture working volumes. As cultured cells, and larger molecules, are retained within a fraction of the system volume, via a semipermeable membrane it may be possible to reduce protein consumption by limiting supplementation to only this fraction. Typically, HFBRs are complex perfusion systems having total volumes incompatible with bench scale screening and optimization of stem cell-based cultures. In this article we describe the use of a simplified HFBR system to assess the feasibility of this technology to produce blood products from umbilical cord blood-derived CD34+ hematopoietic stem progenitor cells (HSPCs). Unlike conventional HFBR systems used for protein manufacture, where cells are cultured in the extracapillary space, we have cultured cells in the intracapillary space, which is likely more compatible with the large-scale production of blood cell suspension cultures. Using this platform we direct HSPCs down the myeloid lineage, while targeting a 100-fold increase in cell density and the use of protein-free bulk medium. Our results demonstrate the potential of this system to deliver high cell densities, even in the absence of protein supplementation of the bulk medium.

An investigation into factors affecting electron density calibration for a megavoltage cone-beam CT system

There is a growing interest in the use of megavoltage cone-beam computed tomography (MV CBCT) data for radiotherapy treatment planning. To calculate accurate dose distributions, knowledge of the electron density (ED) of the tissues being irradiated is required. In the case of MV CBCT, it is necessary to determine a calibration-relating CT number to ED, utilizing the photon beam produced for MV CBCT. A number of different parameters can affect this calibration. This study was undertaken on the Siemens MV CBCT system, MVision, to evaluate the effect of the following parameters on the reconstructed CT pixel value to ED calibration: the number of monitor units (MUs) used (5, 8, 15 and 60 MUs), the image reconstruction filter (head and neck, and pelvis), reconstruction matrix size (256 by 256 and 512 by 512), and the addition of extra solid water surrounding the ED phantom. A Gammex electron density CT phantom containing EDs from 0.292 to 1.707 was imaged under each of these conditions. The linear relationship between MV CBCT pixel value and ED was demonstrated for all MU settings and over the range of EDs. Changes in MU number did not dramatically alter the MV CBCT ED calibration. The use of different reconstruction filters was found to affect the MV CBCT ED calibration, as was the addition of solid water surrounding the phantom. Dose distributions from treatment plans calculated with simulated image data from a 15 MU head and neck reconstruction filter MV CBCT image and a MV CBCT ED calibration curve from the image data parameters and a 15 MU pelvis reconstruction filter showed small and clinically insignificant differences. Thus, the use of a single MV CBCT ED calibration curve is unlikely to result in any clinical differences. However, to ensure minimal uncertainties in dose reporting, MV CBCT ED calibration measurements could be carried out using parameter-specific calibration measurements.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Factors affecting two- and five-year re-offence rates in Queensland drink drivers

Risk factors for repeat drink driving, an important road safety issue, are well known, but estimates of Australian recidivism rates by risk factors, apart from a recent NSW study, are not. Driving records of a cohort of Queensland drink drivers matched by age, region, BAC level and prior offence to participants in a drink driving rehabilitation program were used to estimate sex-specific two- and five-year re-offence rates overall and by these factors. Estimates of the proportion of Queensland drink drivers with a prior DD offence in 2004 were used to standardise rates to the Queensland drink driving population. Rates were higher in remote areas, as were rates in males, young drivers, drivers with high BAC levels and in drivers with one and especially with at least two prior DD convictions. Five-year rates for Queensland were estimated as 21.8% in males and 16.4% in females, appreciably higher than in NSW.

Numerical simulation of red blood cells' deformation using SPH method

A numerical simulation method for the Red Blood Cells’ (RBC) deformation is presented in this study. The two-dimensional RBC membrane is modeled by the spring network, where the elastic stretch/compression energy and the bending energy are considered with the constraint of constant RBC surface area. Smoothed Particle Hydrodynamics (SPH) method is used to solve the Navier-Stokes equation coupled with the Plasma-RBC membrane and Cytoplasm- RBC membrane interaction. To verify the method, the motion of a single RBC is simulated in Poiseuille flow and compared with the results reported earlier. Typical motion and deformation mechanism of the RBC is observed.

The effect of Tai Chi on health related quality of life in people with elevated blood glucose or diabetes : a randomized controlled trial

Purpose The aim was to assess the effects of a Tai Chi based program on health related quality of life (HR-QOL) in people with elevated blood glucose or diabetes who were not on medication for glucose control. Method 41 participants were randomly allocated to either a Tai Chi intervention group (N = 20) or a usual medical care control group (N = 21). The Tai Chi group involved 3 x 1.5 hour supervised and group-based training sessions per week for 12 weeks. Indicators of HR-QOL were assessed by self-report survey immediately prior to and after the intervention. Results There were significant improvements in favour of the Tai Chi group for the SF36 subscales of physical functioning (mean difference = 5.46, 95% CI = 1.35-9.57, P < 0.05), role physical (mean difference = 18.60, 95% CI = 2.16-35.05, P < 0.05), bodily pain (mean difference = 9.88, 95%CI = 2.06-17.69, P < 0.05) and vitality (mean difference = 9.96, 95% CI = 0.77-19.15, P < 0.05). Conclusions The findings show that this Tai Chi program improved indicators of HR-QOL including physical functioning, role physical, bodily pain and vitality in people with elevated blood glucose or diabetes who were not on diabetes medication.