Performance of a point-of-care device for oral fluid ketamine evaluated by a liquid chromatography-tandem mass spectrometry method.

The performance of a point-of-care device, the OratectXP Oral Fluid Drug Screen Device for Ketamine, was evaluated. The cutoff specification for the device was for ketamine at 15 ng/mL. A total of 72 authentic oral fluid samples were collected from volunteers at two local rehabilitation centers for clients with addiction to drugs of abuse. These samples were tested with the device for visual detection of ketamine and also measured by a liquid chromatography isotope-dilution tandem mass spectrometry method for ketamine, norketamine and dehydronorketamine concentrations. Sensitivity of the device was 87.5% when tested by 24 authentic oral fluid samples with ketamine concentrations ≥ 15 ng/mL. False positive rate of the device was 4.5%. Specificity of the device was 97.9% when tested by 48 authentic oral fluid samples with ketamine concentrations < 15 ng/mL. False negative rate of the device was 6%. The overall efficiency of the device was 94%. According to the desirable acceptance criteria proposed by the "Driving Under the Influence of Drugs, Alcohol, and Medicines" project, the performance of the OratectXP was satisfactory and achieved the minimum standard for testing drivers under the influence of drugs. Furthermore, we propose the confirmation cutoff level for oral fluid ketamine to be at 25 ng/mL.

Positive impact of a long-running urban Aboriginal medical service midwifery program.

BACKGROUND: The Winnunga Nimmityjah Aboriginal Health Service Aboriginal Midwifery Access Program (AMAP) was established in 2001 to provide antenatal care, birth support and postnatal care to clients in the Australian Capital Territory (ACT). AIM: To describe the uptake and impact of AMAP services on access to antenatal care, behavioural risk factors and pregnancy outcomes and to compare the characteristics of AMAP clients with other women giving birth in the ACT. METHODS: A descriptive study of medical records for AMAP clients who gave birth in 2004-2008. OUTCOME MEASURES: maternal and baby characteristics, antenatal visits, behavioural risk factors and complications. Characteristics of AMAP clients were compared with the ACT Maternal and Perinatal Collection. RESULTS: Of 187 women, 11.2% were aged <20 years, 50.3% presented in the first trimester and 94.7% attended five or more antenatal visits. Of 193 babies, 17.1% were born preterm and 18.1% had low birthweight. Compared with the ACT Maternal and Perinatal Collection, Aboriginal and Torres Strait Islander AMAP clients had a higher smoking rate (63.8 vs 49.0%), a lower caesarean delivery rate (20.0 vs 27.6%), a slightly lower proportion of preterm babies (18.8 vs 21.6%) and a slightly lower proportion of low-birthweight babies (18.8 vs 21.0%). CONCLUSIONS: Aboriginal Midwifery Access Program provides high-quality antenatal care in a trusted environment. The high rate of smoking in pregnancy needs to be addressed.

Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS.

During evolutionary adaptation in the immune system, host defense is traded off against autoreactivity. Signals through the costimulatory receptor CD28 enable T cells to respond specifically to pathogens, whereas those through the related costimulatory receptor, ICOS, which arose by gene duplication, are critical for affinity maturation and memory antibody responses. ICOS ligand, unlike the pathogen-inducible CD28 ligands, is widely and constitutively expressed in the immune system. Here, we show that crosstalk between these two pathways provides a mechanism for obviating the normal T cell dependence on CD28. Several CD28-mediated responses-generation of follicular helper T cells, germinal center formation, T helper 1 cell-dependent extrafollicular antibody responses to Salmonella and bacterial clearance, and regulatory T cell homeostasis-became independent of CD28 and dependent on ICOS when the E3 ubiquitin ligase Roquin was mutated. Mechanisms to functionally compartmentalize ICOS and CD28 signals are thus critical for two-signal control of normal immune reactions.

Follicular helper T cells are required for systemic autoimmunity.

Production of high-affinity pathogenic autoantibodies appears to be central to the pathogenesis of lupus. Because normal high-affinity antibodies arise from germinal centers (GCs), aberrant selection of GC B cells, caused by either failure of negative selection or enhanced positive selection by follicular helper T (T(FH)) cells, is a plausible explanation for these autoantibodies. Mice homozygous for the san allele of Roquin, which encodes a RING-type ubiquitin ligase, develop GCs in the absence of foreign antigen, excessive T(FH) cell numbers, and features of lupus. We postulated a positive selection defect in GCs to account for autoantibodies. We first demonstrate that autoimmunity in Roquin(san/san) (sanroque) mice is GC dependent: deletion of one allele of Bcl6 specifically reduces the number of GC cells, ameliorating pathology. We show that Roquin(san) acts autonomously to cause accumulation of T(FH) cells. Introduction of a null allele of the signaling lymphocyte activation molecule family adaptor Sap into the sanroque background resulted in a substantial and selective reduction in sanroque T(FH) cells, and abrogated formation of GCs, autoantibody formation, and renal pathology. In contrast, adoptive transfer of sanroque T(FH) cells led to spontaneous GC formation. These findings identify T(FH) dysfunction within GCs and aberrant positive selection as a pathway to systemic autoimmunity.

Oral fluid drug tests: effects of adulterants and foodstuffs.

An on-site oral fluid drug screen, Oratect, was used to investigate the effects of adulterants and foodstuffs on oral fluid test results. Common foods, beverages, food ingredients, cosmetics and hygienic products were demonstrated not to cause false positive results when tested 30 min after their consumption. Evaluations of two commercial oral fluid adulterants, "Clear Choice Fizzy Flush" and "Test'in Spit n Kleen Mouthwash" suggest their mechanism of action is the clearing of residual drugs of abuse compounds through rinsing of the oral cavity. They do not directly destroy the drug compounds or change the pH of the oral fluid. It is also suggested that a common mouthwash would perform similar action.