Endocrine control of mucosal immunity in the female reproductive tract: impact of environmental disruptors

The complexity of the human female reproductive tract (FRT) with its multiple levels of hormonally controlled immune protection has only begun to be understood. Dissecting the functions and roles of the immune system in the FRT is complicated by the differential hormonal regulation of its distinct anatomical structures that vary throughout the menstrual cycle. Although many fundamental mechanisms of steroid regulation of reproductive tract immune function have been determined, the effects of exogenous synthetic steroids or endocrine disruptors on immune function and disease susceptibility in the FRT have yet to be evaluated in detail. There is increasing evidence that environmental or synthetic molecules can alter normal immune function. This review provides an overview of the innate and adaptive immune systems, the current status of immune function in the FRT and the potential risks of environmental or pharmacological molecules that may perturb this system.     

Electronic prescribing and other forms of technology to reduce inappropriate medication use and polypharmacy in older people: a review of current evidence

This review provided an overview of the current evidence in relation to the use of e-prescribing and other forms of technology, such as CDSS, to reduce inappropriate prescribing in older people. The evidence indicates that various types of e-prescribing and CDSS interventions have the potential to reduce inappropriate prescribing and polypharmacy in older people, but the magnitude of their effect varies according to study design and setting. There was significant heterogeneity in the studies reported in terms of study designs, intervention design, patient settings, and outcome measures with patient outcomes seldom reported. Widespread diffusion of these interventions has not occurred in any of the health care settings examined. Overall, health care providers report being satisfied with e-prescribing systems and see the systems as having a positive impact on the safety of their prescribing practices, yet the problem of overriding or ignoring alerts persists. The problem of large numbers of inaccurate and insignificant alerts and this issue, along with the other barriers that have been identified, warrant further investigation.     

Three-Dimensional CT Volumetry Predicts Outcome of Laparoscopic Splenectomy for Splenomegaly: Retrospective Clinical Study

Background

The aim of this study was to determine the predictive value of the preoperative three-dimensional reconstructed volume (3D volumetry) for outcomes of laparoscopic splenectomy. The impact of splenomegaly on the feasibility of laparoscopic splenectomy is still debated. We hypothesized that splenic volumetry may accurately estimate splenic volume preoperatively and be used by surgeons to select patients for laparoscopic splenectomy.

Methods

We performed a retrospective review of 88 patients seen at a tertiary referral center undergoing laparoscopic or open splenectomy between 2001 and 2010. Patients included in the study underwent elective splenectomy without associated procedures and had preoperative imaging available at our institution. We evaluated clinical, demographic characteristics and perioperative imaging as predictors of outcome. Study endpoints included conversion to open splenectomy, operating time, estimated blood loss (EBL), length of stay (LOS), postoperative complications, and mortality.

Results

In all, 53 procedures were started laparoscopically. Among them, 7 (13.2 %) were converted to open splenectomy and 7 (13.2 %) to hand-assisted laparoscopic splenectomy. The conversion group was matched with 35 patients who underwent open splenectomy to determine differences in outcomes between these groups. There were no conversions in spleens measuring <1100 cc, whereas spleens of 1100 to 2700 cc had a conversion rate of 41 %. Spleen volume >2700 cc was associated with an 87.5 % conversion rate. Spleen 3D volumetry >2700 cc was the only independent predictor of surgical conversion on multivariate analysis (odds ratio 38.0, confidence interval 4.02–358.75, p = 0.001). Patients who underwent open splenectomy had shorter operating times (160.3 vs. 253.0 min, p = 0.001) than those converted from laparoscopic to open splenectomy.

Conclusions

A 3D reconstructed splenic volume of >2700 cc is a predictor of conversion from laparoscopic to open splenectomy. For spleens measuring <2700 cc, laparoscopic splenectomy may be performed by experienced surgeons with low to moderate rates of conversion. For spleens with a 3D reconstructed volume >2700 cc, laparoscopic splenectomy is associated with high rates of conversion to open surgery.     

Development of Stabilizing Formulations of a Trivalent Inactivated Poliovirus Vaccine in a Dried State for Delivery in the Nanopatch™ Microprojection Array

The worldwide switch to inactivated polio vaccines (IPVs) is a key component of the overall strategy to achieve and maintain global polio eradication. To this end, new IPV vaccine delivery systems may enhance patient convenience and compliance. In this work, we examine Nanopatch? (a solid, polymer microprojection array) which offers potential advantages over standard needle/syringe administration including intradermal delivery and reduced antigen doses. Using trivalent IPV (tIPV) and a purpose-built evaporative dry-down system, candidate tIPV formulations were developed to stabilize tIPV during the drying process and on storage. Identifying conditions to minimize tIPV potency losses during rehydration and potency testing was a critical first step. Various classes and types of pharmaceutical excipients (～50 total) were then evaluated to mitigate potency losses (measured through D-antigen ELISAs for IPV1, IPV2, and IPV3) during drying and storage. Various concentrations and combinations of stabilizing additives were optimized in terms of tIPV potency retention, and 2 candidate tIPV formulations containing cyclodextrin and a reducing agent (e.g., glutathione), maintained ≥80% D-antigen potency during drying and subsequent storage for 4 weeks at 4°C, and ≥60% potency for 3 weeks at room temperature with the majority of losses occurring within the first day of storage.     

Effects of a novel antiplatelet agent in mural thrombogenesis on collagen-coated glass

A parallel plate flow chamber and an epifluorescence video microscopy system were used to investigate the inhibitory effect of a novel antiplatelet agent (GT-12), a carbamoylpiperidine congener, on surface platelet aggregation and on the kinetics of thrombus growth induced by collagen-coated glass under controlled flow. Both macroscopic and microscopic measurements revealed that increasing concentrations of the drug correspondingly decreased the reaction rate between platelets at the surface, thereby reducing thrombus rate of growth at the surface. Because of decreased platelet/platelet adhesion, there was some embolization of the larger thrombi near the inlet of the reactive surface. In the presence of GT-12, average thrombus size and number of platelets per thrombus were both strikingly lowered. In addition, the net rate of growth of individual thrombi decreased to zero after short exposure times (about 60 seconds), in sharp contrast to controls. In contrast to chlorpromazine, GT-12 was effective in inhibiting platelet aggregation and thrombus rate of growth at relatively low concentrations (less than 100 mumol/L) in whole blood. The drug's effectiveness relative to controls in impeding platelet/platelet interactions was found to increase with decreasing incubation time and increasing perfusion time.