Pharmacokinetically-based prediction of the effects of antibiotic combinations on resistant Staphylococcus aureus mutants: in vitro model studies with linezolid and rifampicin

To explore if combinations of linezolid (L) with rifampicin (R) are able to restrict Staphylococcus aureus resistance, the enrichment of L- and R-resistant mutants was studied in an in vitro dynamic model. L- and R-resistant mutants were enriched in all single drug treatments. In contrast, L-resistant mutants were not enriched and R-resistant mutants were similar to baseline amounts with only minimal regrowth at the end of the combination treatments. These effects appear to be explained by lowering the mutant prevention concentration (MPC) for L+R combinations (MPC_L+R) compared to the MPCs of L and R alone (MPC_L and MPC_R) and thereby the longer times above MPC_L+R (73–100% of the dosing interval for L and 42–58% for R) compared to the times above MPC_L (0–44%) and MPC_R (0%). These findings provide an opportunity to predict the selection of S. aureus resistance in L+R treatments using MPC_L+Rs.     

Rationale,Procedures, and Response Rates for the 2015 Administration of NCI’s Health Information National Trends Survey: HINTS-FDA 2015

The National Cancer Institute (NCI) developed the Health Information National Trends Survey (HINTS) to monitor population trends in cancer communication practices, information preferences, health risk behaviors, attitudes, and cancer knowledge. The U.S. Food and Drug Administration (FDA) recognized HINTS as a unique data resource for informing its health communication endeavors and partnered with NCI to field HINTS-FDA 2015. HINTS-FDA 2015 was a self-administered paper instrument sent by mail May 29 to September 8, 2015, using a random probability-based sample of U.S. postal addresses stratified by county-level smoking rates, with an oversampling of high and medium-high smoking strata to increase the yield of current smokers responding to the survey. The response rate for HINTS-FDA 2015 was 33% (N = 3,738). The yield of current smokers (n = 495) was lower than expected, but the sampling strategy achieved the goal of obtaining more former smokers (n = 1,132). Public-use HINTS-FDA 2015 data and supporting documentation have been available for download and secondary data analyses since June 2016 at http://hints.cancer.gov. NCI and FDA encourage the use of HINTS-FDA for health communication research and practice related to tobacco-related communications, public knowledge, and behaviors as well as beliefs and actions related to medical products and dietary supplements.     

Drug Trial: A Comparison between the Topical Efficacy of 1% Hydrocortisone and 0.2% Fluocortolone

A trial has been carried out to compare the relative efficacy of 1% hydrocortisone with 0.2% fluocortolone applied topically using the blind paired comparison method with a randomized series of out-patients with bilateral symmetrical lesions of eczema and psoriasis. Results show a significant preference for 0.2% fluocortolone over 1%, hydrocortisone in cases of eczema and no preference in psoriasis.     

Magnetic resonance microscopy of human and porcine neurons and cellular processes

With its unparalleled ability to safely generate high-contrast images of soft tissues, magnetic resonance imaging (MRI) has remained at the forefront of diagnostic clinical medicine. Unfortunately due to resolution limitations, clinical scans are most useful for detecting macroscopic structural changes associated with a small number of pathologies. Moreover, due to a longstanding inability to directly observe magnetic resonance (MR) signal behavior at the cellular level, such information is poorly characterized and generally must be inferred. With the advent of the MR microscope in 1986 came the ability to measure MR signal properties of theretofore unobservable tissue structures. Recently, further improvements in hardware technology have made possible the ability to visualize mammalian cellular structure. In the current study, we expand upon previous work by imaging the neuronal cell bodies and processes of human and porcine α-motor neurons. Complimentary imaging studies are conducted in pig tissue in order to demonstrate qualitative similarities to human samples. Also, apparent diffusion coefficient (ADC) maps were generated inside porcine α-motor neuron cell bodies and portions of their largest processes (mean=1.7 ± 0.5 μm2/ms based on 53 pixels) as well as in areas containing a mixture of extracellular space, microvasculature, and neuropil (0.59 ± 0.37 μm2/ms based on 33 pixels). Three-dimensional reconstruction of MR images containing α-motor neurons shows the spatial arrangement of neuronal projections between adjacent cells. Such advancements in imaging portend the ability to construct accurate models of MR signal behavior based on direct observation and measurement of the components which comprise functional tissues. These tools would not only be useful for improving our interpretation of macroscopic MRI performed in the clinic, but they could potentially be used to develop new methods of differential diagnosis to aid in the early detection of a multitude of neuropathologies.     

Incidence of systemic reactions during rush immunotherapy.

Rush immunotherapy (RIT) was administered on an outpatient basis to 11 patients. Of these, nine had asthma and four were steroid-dependent. All patients received extracts containing a mixture of antigens to which they were prick-sensitive. FEV1s were greater than 80% predicted before starting RIT. Four patients each required a 1 week steroid "burst" to accomplish this. A series of 8 subcutaneous injections were given starting with 0.3 mL of 1:100,000 (wt/vol) and ending with 0.10 mL of 1:100 (wt/vol) 1.5 days later. A dose of 0.15 mL of 1:100 was given weekly after that. All patients but one completed the RIT. Four had sore arms, four had pruritus and/or sneezing, four developed wheezing, and one experienced anaphylaxis with hypotension. Systemic reactions tended to occur at the higher doses and usually more than 30 minutes after a previous injection. Subsequent weekly injections were tolerated without reactions by seven of the patients. Rush immunotherapy is an effective method for administering a high dose of allergen in a very short time period. Due to the risk of systemic reactions it needs to be given under carefully controlled conditions.     

A non-cholinergic function for acetylcholinesterase in the substantia nigra: Behavioural evidence

Summary Acetylcholinesterase is released from substantia nigra neurons, independently of cholinergic transmission. In an attempt to discover the functional significance of this phenomenon, the behavioural effects of injecting acetylcholinesterase into one substantia nigra of the rat were investigated. Following a single injection of the enzyme, intraperitoneal amphetamine evoked circling behaviour in a direction away from the side of injection. Purified acetylcholinesterase with a similar electrophoretic mobility to the endogenous secreted form, was far more potent in eliciting circling than much higher activities of commercial enzyme, consisting of several molecular species of acetylcholinesterase. Similar infusions of butyrylcholinesterase did not induce circling. Depending upon the amount of enzyme initially given, the behavioural effects of a single injection of acetylcholinesterase persisted for up to thirty days. During this period apomorphine, administered systemically, induced transient circling towards the acetylcholinesterase-treated side. It is concluded that secreted acetylcholinesterase has a functional significance within the substantia nigra, independent of cholinergic transmission. This released enzyme could exert long-term changes in the activity of the nigrostriatal system, involving modification of dopamine striatal receptors.This work was supported by the M.R.C., Project Grant G810/ 79/93 N.     

Outdoor dynamic subject-specific evaluation of internal stresses in the residual limb: hydraulic energy-stored prosthetic foot compared to conventional energy-stored prosthetic feet

The prosthetic foot plays an important role in propelling, breaking, balancing and supporting body loads while the amputee ambulates on different grounds. It is therefore important to quantify the effect of the prosthetic foot mechanism on biomechanical parameters, in order to prevent pressure ulcers and deep tissue injury. Our aim was to monitor the internal stresses in the residuum of transtibial amputation (TTA) prosthetic-users ambulating on different terrains, which the amputees encounter during their daily activities, i.e. paved floor, grass, ascending and descending stairs and slope. We specifically aimed to compare between the internal stresses in the TTA residuum of amputees ambulating with a novel hydraulic prosthetic foot compared to conventional energy storage and return (ESR) prosthetic feet. Monitoring of internal stresses was accomplished using a portable subject-specific real-time internal stress monitor. We found significant decrease (p<0.01) in peak internal stresses and in the loading rate of the amputated limb, while walking with the hydraulic foot, compared to walking with ESR feet. The loading rate calculated while ambulating with the hydraulic foot was at least three times lower than the loading rate calculated while ambulating with the ESR foot. Although the average decrease in internal stresses was ≈ 2-fold larger when replacing single-toe ESR feet with the hydraulic foot than when replacing split-toed ESR feet with the hydraulic foot, the differences were statistically insignificant. Our findings suggest that using a hydraulic prosthetic foot may protect the distal tibial end of the TTA residuum from high stresses, therefore preventing pressure-related injury and pain.