Surface Point Cloud Ultrasound with Transcranial Doppler: Coregistration of Surface Point Cloud Ultrasound with Magnetic Resonance Angiography for Improved Reproducibility, Visualization, and Navigation in Transcranial Doppler Ultrasound.

Transcranial Doppler (TCD) ultrasound is a standard tool used in the setting of recent sub-arachnoid hemorrhage (SAH). By tracking velocity in the circle-of-Willis vessels, vasospasm can be detected as interval velocity increase. For this disease process, repeated TCD velocity measurements over many days is the basis for its usefulness. However, a key limitation to TCD is its user dependence, which is itself largely due to the fact that exact information about probe positioning is lost between subsequent scans. Surface point cloud ultrasound (SPC-US) was recently introduced as a general approach combining ultrasound and three-dimensional surface imaging of patient + probe. In the present proof-of-principle demonstration, we have applied SPC-US to TCD and co-registered the skin surface with that from MRA images to provide a roadmap of the vasculature in 3D space for better speed, accuracy, reproducibility, and potential semi-automation of TCD. Collating the acronyms, we call the combined approach SPC-US-TCD. TCD of the M1 was obtained while three-dimensional photographic images were obtained with the Structure Sensor camera. MRA imaging was also obtained. SPC-US-TCD and corresponding MRA 3D reconstruction images were co-registered in MeshMixer using the skin surfaces for alignment. A cylinder the width of the TCD probe was placed over the fused images and aligned with the direction and orientation of the TCD probe to demonstrate the acoustic beam. In the fused images, the acoustic beam intersects the right M1 segment of the middle cerebral artery (MCA). The angle of insonation is well demonstrated and measurable in various planes. Distance measurements made in Blender localized the TCD probe position based on three skin surface landmarks, and tabulated orientation based on three angles along the corresponding directions. SPC-US-TCD provides valuable information that is otherwise not present in TCD studies. By co-registering SPC-US-TCD data with that from cross sectional vessel imaging, precise probe location relative to external skin surface landmarks as well as 3D vessel location relative to TCD probe placement offers the potential to provide a roadmap that improves exam reproducibility, speed of acquisition, and accuracy. The goal of future work is to demonstrate this improvement statistically by application to multiple patients and scans.

Systemic immunosuppression by methylprednisolone and pregnancy rates in goats undergoing the transfer of cloned embryos.

The presence of the zona pellucida has been perceived as a requirement for the oviductal transfer of cloned embryos at early stages of development while protecting the embryo from an immune system response. We hypothesized that steroid hormone therapy could reduce a potential cellular immune response after the transfer of zona-free cloned embryos into the oviduct of recipient female goats. In Experiment 1, seven does were used to study the systemic immunosuppressant effect of the methylprednisolone administration (for 3 days) on blood cell counts. Whole blood was collected prior to treatment with methyprednisolone and then on Days 1, 2, 3, 4, 7, 14, 21 and 28 after the first dose of methylprednisolone for the analysis of haematological parameters. Methylprednisolone treatment significantly reduced circulating white blood cells and neutrophils in comparison with pre-treatment levels, demonstrating a systemic immunosuppressant effect. In Experiment 2, a group of 58 does were used as recipient females to study the effect of administration of methylprednisolone for 3 days on the establishment of pregnancies after the transfer of zona-free cloned embryos into the oviducts. No effects on pregnancy rates on Day 30 were observed regarding the distinct treatment groups (control vs. methylprednisolone), the source of oocytes (in vivo- vs in vitro-matured) or the presence or absence of the zona pellucida in embryos. In summary, methylprednisolone was effective at inducing a systemic immunosuppressed state in goats, but the treatment prior to embryo transfer did not affect pregnancy rates. Moreover, pregnancy rates were similar between zona-free and zona-intact goat cloned embryos.

A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Plasmodium vivax Hypnozoites.

Radical cure of Plasmodium vivax malaria must include elimination of quiescent 'hypnozoite' forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets for hypnozoites, we screened the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library and a collection of epigenetic inhibitors against P. vivax liver stages. From both libraries, we identified inhibitors targeting epigenetics pathways as selectively active against P. vivax and P. cynomolgi hypnozoites. These include DNA methyltransferase (DNMT) inhibitors as well as several inhibitors targeting histone post-translational modifications. Immunofluorescence staining of Plasmodium liver forms showed strong nuclear 5-methylcystosine signal, indicating liver stage parasite DNA is methylated. Using bisulfite sequencing, we mapped genomic DNA methylation in sporozoites, revealing DNA methylation signals in most coding genes. We also demonstrated that methylation level in proximal promoter regions as well as in the first exon of the genes may affect, at least partially, gene expression in P. vivax. The importance of selective inhibitors targeting epigenetic features on hypnozoites was validated using MMV019721, an acetyl-CoA synthetase inhibitor that affects histone acetylation and was previously reported as active against P. falciparum blood stages. In summary, our data indicate that several epigenetic mechanisms are likely modulating hypnozoite formation or persistence and provide an avenue for the discovery and development of improved radical cure antimalarials.

Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a Phase 3, multicentre, double-blind, randomized study.

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are causing serious nosocomial infections. Tigecycline was evaluated in hospitalized patients with MRSA or VRE infection. PATIENTS AND METHODS: A randomized (3:1), double-blind, multicentre, Phase 3 study compared the safety and efficacy of tigecycline with vancomycin or linezolid in hospitalized patients with MRSA or VRE infection, respectively. Patients were treated for 7-28 days and the test-of-cure (TOC) assessment was made 12-37 days after the last dose. The primary efficacy endpoint was the clinical response (cure, failure and indeterminate) in the co-primary, microbiologically evaluable (ME) and microbiologically modified intent-to-treat (m-mITT) populations at the TOC assessment. RESULTS: For MRSA infection, clinical cure rates in the ME population (n = 117) were 81.4% (70 of 86 patients) with tigecycline and 83.9% (26 of 31 patients) with vancomycin. In the m-mITT population (n = 133), clinical cure occurred in 75 of 100 tigecycline-treated patients (75.0%) and in 27 of 33 vancomycin-treated patients (81.8%). In patients with complicated skin and skin structure infections caused by MRSA, cure rates were similar with tigecycline or vancomycin (86.4% versus 86.9% in ME population; and 78.6% versus 87.0% in m-mITT population). In patients with MRSA infection, nausea or vomiting occurred more frequently with tigecycline than with vancomycin (41.0% versus 17.9%); most cases were mild, with only three patients discontinuing treatment. In patients with VRE (total enrollment, 15), 3 of 3 and 3 of 8 patients in the ME and m-mITT populations, respectively, were cured by tigecycline, compared with 2 of 3 patients in the ME and m-mITT populations treated with linezolid. CONCLUSIONS: Tigecycline is safe and effective in hospitalized patients with serious infection caused by MRSA. There were too few cases of VRE to draw any conclusions.

Analysis of the rainbow trout solute carrier 11 family reveals iron import < or = pH 7.4 and a functional isoform lacking transmembrane domains 11 and 12.

A Xenopus oocyte heterologous expression system was used to characterise iron transport properties of two members of the solute carrier 11 (slc11) protein family isolated from rainbow trout gills. One cDNA clone differed from the trout Slc11alpha containing an additional 52bp in the exon between transmembrane domains (TM) 10 and 11. The 52bp contained a stop codon, resulting in a novel isoform lacking the last two TM (termed slc11gamma). Slc11gamma and another isoform slc11beta, import Fe(2+) at external pHs < or = to 7.4. Trout slc11beta Fe(2+) import was more sensitive to inhibition by divalent metals. The novel vertebrate slc11gamma isoform functions without TM11 and 12.

The effects of dietary iron concentration on gastrointestinal and branchial assimilation of both iron and cadmium in zebrafish (Danio rerio).

Zebrafish (Danio rerio) were fed either a diet containing 33mgFekg(-1) (low) or 95mgFekg(-1) (normal) for 10 weeks, after which short-term Cd and Fe uptake by the gastrointestinal tract and gill was assessed. Carcass metal content and transcript levels of the iron importer, Divalent Metal Transporter 1 (DMT1) and an iron exporter, ferroportin1, in both the gastrointestinal tract and gill were also measured. Fish fed the low Fe diet accumulated 13 times more Cd into their livers via the gastrointestinal tract than those fed the normal Fe diet. However, no significant increase in liver Fe accumulation was measured. Concomitantly, when exposed to 48nmolCdL(-1) fish fed the low Fe diet exhibited a approximately 4-fold increase in Cd accumulation on the gill and in the liver, compared to those fed a normal diet. In addition, fish fed the low Fe diet also significantly accumulated more Fe on the gill (nine-fold increase) and into the carcass (four-fold increase) when exposed to 96nmolFeL(-1), compared to fish fed a normal diet. Surprisingly, carcass Fe, Ca and Mg concentrations were increased in fish fed the low Fe diet, which suggests that Fe body levels may not be a good indicator of whether a fish is more or less susceptible to increased non-essential metal accumulation via an Fe uptake pathway. However, significantly elevated transcript levels of DMT1 and ferroportin1 (2.7- and 3.8-fold induction, respectively) were seen in the gastrointestinal tract, and DMT1 in the gills (1.8-fold induction) of zebrafish fed a low Fe diet. The correlation between Cd uptake and DMT1 expression suggests that one route of uptake of Cd, either from the diet or from the water, could be via DMT1.

GlycoSuiteDB: a new curated relational database of glycoprotein glycan structures and their biological sources.

GlycoSuiteDB is a relational database that curates information from the scientific literature on glyco-protein derived glycan structures, their biological sources, the references in which the glycan was described and the methods used to determine the glycan structure. To date, the database includes most published O:-linked oligosaccharides from the last 50 years and most N:-linked oligosaccharides that were published in the 1990s. For each structure, information is available concerning the glycan type, linkage and anomeric configuration, mass and composition. Detailed information is also provided on native and recombinant sources, including tissue and/or cell type, cell line, strain and disease state. Where known, the proteins to which the glycan structures are attached are reported, and cross-references to the SWISS-PROT/TrEMBL protein sequence databases are given if applicable. The GlycoSuiteDB annotations include literature references which are linked to PubMed, and detailed information on the methods used to determine each glycan structure are noted to help the user assess the quality of the structural assignment. GlycoSuiteDB has a user-friendly web interface which allows the researcher to query the database using mono-isotopic or average mass, monosaccharide composition, glycosylation linkages (e.g. N:- or O:-linked), reducing terminal sugar, attached protein, taxonomy, tissue or cell type and GlycoSuiteDB accession number. Advanced queries using combinations of these parameters are also possible. GlycoSuiteDB can be accessed on the web at http://www.glycosuite.com.

Differential roles of inflammation and apoptosis in initiation of mid-gestational abortion in malaria-infected C57BL/6 and A/J mice.

INTRODUCTION: Plasmodium chabaudi AS-infection in pregnant A/J and C57BL/6J mice results in mid-gestational pregnancy loss. Although associated with increased systemic and placental pro-inflammatory responses and coagulopathy, the molecular mechanisms that underlie poor pregnancy outcomes in these mice are not yet fully understood. This study investigates the relationships between inflammation, apoptosis and malaria-induced pregnancy loss. METHODS: Infection with P. chabaudi AS in early murine pregnancy and term human placental tissues from an endemic setting were assessed by histology, immunohistochemistry, TUNEL staining, real-time PCR, flow cytometry, western blot, and ELISA. RESULTS: Quantitative PCR reveals accumulation of lymphocytes and monocytes and upregulation of chemokines that attract these cell types in malaria-exposed mid-gestational A/J conceptuses. Monocyte accumulation is confirmed by flow cytometry and placental immunohistochemistry. Concurrent with initiation of malaria-induced abortion, markers of apoptosis are evident in the junctional zone, but not the labyrinth, of A/J placentae. In contrast, mid-gestation conceptuses in infected C57BL/6J lack evidence for monocyte accumulation, exhibiting low or no in situ placental staining despite trophoblast immunoreactivity for the monokine, CCL2. Additionally, placental apoptosis is not consistently observed, and when evident, appears after malaria-induced abortion typically initiates. Similarly, trophoblast apoptosis in term human placental malaria is not observed. Of those studied, a sole common feature of malaria-induced abortion in A/J and C57BL/6J mice is elevation of plasma tumor necrosis factor. DISCUSSION: Consistent with our previous observations, tumor necrosis factor is likely to be a central driver of malaria-induced pregnancy loss in both strains, but likely operates through mechanisms distinct from placental apoptosis in C57BL/6J mice.

Use of flurbiprofen to inhibit corneal neovascularization.

Following the suggestion that prostaglandins are involved in corneal neovascularization, two inhibitors of prostaglandin formation, prednisolone acetate and flurbiprofen sodium, have been evaluated in two experimental models of corneal neovascularization. The fatty acid cyclooxygenase inhibitor, flurbiprofen, at concentrations of 0.01% and 0.1%, significantly decreased the rate of vessel growth compared with vehicle controls in both silver nitrate cauterization and anterior chamber alloxan models of corneal neovascularization. Prednisolone, at a concentration of 1%, was used as a positive control. It did inhibit neovascularization in the latter model, but was ineffective in the former. It is concluded that 0.1% flurbiprofen is equipotent to 1% prednisolone as an inhibitor of corneal neovascularization. The mechanism is unknown but is likely to be via inhibition of prostaglandin formation and/or inhibition of leukocytic infiltration.

Optimal control of artificial aeration in river networks.

Under suitable conditions, artificial in situ aeration is an appropriate and economical method of alleviating water pollution. Regional planning for the control of water pollution can properly consider the use of artificial aeration on a river network in conjunction with other pollution abatement techniques. Application of optimization methods can yield significant savings in the aeration energy consumption required to produce a given level of impact on a polluted river network. The confluence of two rivers, each receiving effluent discharges and subject to artificial aeration control, is first investigated. It is shown that the optimal feedback aeration strategy in one branch of the river system not only depends on measurements of the water quality in that branch, but also on the water quality measurements in the second branch. With these results as the foundation, the optimal aeration control strategy is then determined for a generalized river network modeled as a graphical tree. Various properties of the optimal aeration policy are illustrated by computational examples.

Pharmacy-nursing report form used to monitor and adjust schedules of large volume parenteral solutions.

The use of an i.v. report form to regularly monitor and adjust the schedules of large volume parenteral solutions and irrigations is discussed. The departments of pharmaceutical services and nursing instituted a program that allowed both departments to compare the schedules of large volume parenterals and irrigations for each shift. This program centers around the use of an i.v. report form, for which clinical nurses record information concerning the progress of i.v. fluids and irrigations. The completed report is forwarded to the pharmacy, where pharmacy personnel use the information to continually update i.v. therapy profiles and adjust the administration schedules of subsequent solutions. Pharmacy's review of the i.v. report form allows the pharmacist to use his/her clinical judgment concerning the appropriateness of therapy and provides an opportunity to prevent and observe medication errors. Although this system has not be formally compared to other systems, it appears that an i.v. report system is an effective means of communication between pharmacy and nursing departments.

Osmoregulatory bicarbonate secretion exploits H(+)-sensitive haemoglobins to autoregulate intestinal O2 delivery in euryhaline teleosts.

Marine teleost fish secrete bicarbonate (HCO3 (-)) into the intestine to aid osmoregulation and limit Ca(2+) uptake by carbonate precipitation. Intestinal HCO3 (-) secretion is associated with an equimolar transport of protons (H(+)) into the blood, both being proportional to environmental salinity. We hypothesized that the H(+)-sensitive haemoglobin (Hb) system of seawater teleosts could be exploited via the Bohr and/or Root effects (reduced Hb-O2 affinity and/or capacity with decreasing pH) to improve O2 delivery to intestinal cells during high metabolic demand associated with osmoregulation. To test this, we characterized H(+) equilibria and gas exchange properties of European flounder (Platichthys flesus) haemoglobin and constructed a model incorporating these values, intestinal blood flow rates and arterial-venous acidification at three different environmental salinities (33, 60 and 90). The model suggested red blood cell pH (pHi) during passage through intestinal capillaries could be reduced by 0.14-0.33 units (depending on external salinity) which is sufficient to activate the Bohr effect (Bohr coefficient of -0.63), and perhaps even the Root effect, and enhance tissue O2 delivery by up to 42 % without changing blood flow. In vivo measurements of intestinal venous blood pH were not possible in flounder but were in seawater-acclimated rainbow trout which confirmed a blood acidification of no less than 0.2 units (equivalent to -0.12 for pHi). When using trout-specific values for the model variables, predicted values were consistent with measured in vivo values, further supporting the model. Thus this system is an elegant example of autoregulation: as the need for costly osmoregulatory processes (including HCO3 (-) secretion) increases at higher environmental salinity, so does the enhancement of O2 delivery to the intestine via a localized acidosis and the Bohr (and possibly Root) effect.

Cutaneous vasoregulation during short- and long-term aerial acclimation in the amphibious mangrove rivulus, Kryptolebias marmoratus.

The mangrove rivulus (Kryptolebias marmoratus) is an amphibious fish and evidence suggests that the cutaneous surface is the primary site of gas exchange during emersion. The aim of this study was to determine whether cutaneous blood vessels were regulated in the caudal fin during the initial transition from water to aerial exposure, and after 10 days of aerial acclimation. Acute changes (first 3 min following emersion) in the cutaneous vessels diameter were measured in real-time on live fish using light microscopy. The data show that under control conditions, only arterioles in the caudal fin were vasoactive. During the first 20s of aerial acclimation the arterioles significantly constricted (-2.1 ± 0.4 µm), which was followed immediately by a relaxation (from 40 to 180 s). This vasoconstriction was eliminated with the addition of phentolamine (50 µmoll(-1)), which indicates that the vasoconstriction was mediated by α-adrenoreceptors. Longer-term changes in the cutaneous surface vasculature were determined using fluorescent immunohistochemistry and antibodies for the endothelial marker, CD31. Fish aerially acclimated for 10 days exhibited significantly higher levels of endothelial fluorescence in the caudal fin when compared to control fish in water, indicating endothelial cell production (i.e. angiogenesis). These data combined show that for every emersion episode, there is an initial α-adrenergic mediated vasoconstriction, which is most likely, a stress response. This is then followed by a long-term acclimation involving an upregulation in endothelial cell production, which would subsequently enhance blood perfusion to the cutaneous surface and potentially increase the capacity for gas exchange with the external environment.

Does laterality of motor impairment tell us something about cognition in Parkinson disease?

This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.

Post-prandial alkaline tide in freshwater rainbow trout: effects of meal anticipation on recovery from acid-base and ion regulatory disturbances.

The post-feeding alkaline tide (elevated blood pH and HCO3-) has been well characterised in air-breathing animals, but to date this phenomenon has only been demonstrated in one piscine species, a marine elasmobranch. We have investigated the acid-base and ion regulatory responses of a freshwater teleost to voluntary feeding as well as to involuntary filling of the stomach via an indwelling gastric intubation tube. One group of rainbow trout (Oncorhynchus mykiss) were fed a 1% body mass ration of homogenised food via the gastric intubation tube. Another group fed voluntarily on a 1% body mass ration. Blood samples were taken via dorsal aortic catheters from fish in both groups before feeding and over the subsequent 72 h. Trout fed via the gastric intubation tube exhibited post-prandial metabolic alkalosis of the blood (pH and plasma HCO3- increases of up to approximately 0.2 pH units and 3 mmol l(-1), respectively), that was more than twofold greater than the voluntary feeding fish, and took three times as long to recover (72 versus 24 h). Arterial PCO2 was unchanged in both groups indicating that freshwater trout do not retain CO2 to compensate for a post-prandial alkaline tide. Although excretion of HCO3- to the water increased post-prandially, NH4+ excretion followed a similar pattern, such that net acid equivalent fluxes were unaffected. Thus, sites other than the gills or kidney must be responsible for recovery of blood acid-base status, with intestinal HCO3- secretion being a likely candidate. In addition, fish fed via the gastric intubation tube experienced a large (17 mmol l(-1)) but acute (6 h) drop in plasma chloride and a very large (53%) and long lasting decline in plasma magnesium concentration, that were absent in voluntarily feeding fish. These results further indicate a potentially important role for neuro-endocrine mediated mechanisms when fish feed voluntarily, in promoting the earlier initiation of compensatory responses that regulate blood ion levels and acid-base status. This aspect should also be considered when interpreting studies on other aspects of post-prandial physiology, where force feeding by gavage is commonly used in preference to voluntary feeding.

The effects of pH and the iron redox state on iron uptake in the intestine of a marine teleost fish, gulf toadfish (Opsanus beta).

In the marine teleost intestine the secretion of bicarbonate increases pH of the lumen (pH 8.4 -9.0) and importantly reduces Ca2+ and Mg2+ concentrations by the formation of insoluble divalent ion carbonates. The alkaline intestinal environment could potentially also cause essential metal carbonate formation reducing bioavailability. Iron accumulation was assessed in the Gulf toadfish (Opsanus beta) gut by mounting intestine segments in modified Ussing chambers fitted to a pH-stat titration system. This system titrates to maintain lumen pH constant and in the process prevents bicarbonate accumulation. The luminal saline pH was clamped to pH 5.5 or 7.0 to investigate the effect of proton concentrations on iron uptake. In addition, redox state was altered (gassing with N2, addition of dithiothreitol (DTT) and ascorbate) to evaluate Fe3+ versus Fe2+ uptake, enabling us to compare a marine teleost intestine model for iron uptake to the mammalian system for non-haem bound iron uptake that occurs via a ferrous/proton (Fe2+/H+) symporter called Divalent Metal Transporter 1 (DMT1). None of the redox altering strategies affected iron (Fe3+ or Fe2+) binding to mucus, but the addition of ascorbate resulted in a 4.6-fold increase in epithelium iron accumulation. This indicates that mucus iron binding is irrespective of valency and suggests that ferrous iron is preferentially transported across the apical surface. Altering luminal saline pH from 7.0 to 5.5 did not affect ferric or ferrous iron uptake, suggesting that if iron is entering via DMT1 in marine fish intestine this transporter works efficiently under circumneutral conditions.

Caregivers' experience of risk in dementia: the LASER-AD study.

The objective was to explore caregivers' experience of and concerns about the safety of care recipients (CRs) with Alzheimer's disease (AD) living at home. We interviewed family caregivers about their concerns regarding CR's safety, occurrence of risk over the last year and safety measures taken to manage risk. A total of 89 family caregiver/CR dyads participated. All had been recruited as part of a larger longitudinal study based in London and South East Region (LASER) of the UK. Caregivers spent a substantial proportion of the day supervising the CR (mean = 15.5 hours). Most caregivers (39; 81.2%) of the 48/89 CRs left alone worried about their safety. Sixty-one (68.5%) caregivers reported at least one incident in which the CR had been at risk within the past year. A majority (71; 79.8%) had taken measures to prevent risk behaviours. Greater impairment in activities of daily living and the caregiver not being the CR's spouse were associated with more measures being taken. Caregivers themselves provide supervision most of the time for the CR, and are worried when they are left alone. This is realistic as despite caregiver's attempts at managing their CR's risks, including direct supervision, dangerous incidents still frequently occur in people with AD.

Delayed conjunctival closure in adjustable strabismus surgery.

Adjustable suture strabismus surgery has proved to be a significant aid in handling difficult strabismus cases, and various methods of conjunctival closure have been discussed. A new method of conjunctival closure, enabling direct visualization and manipulation of the muscle with minimal tissue drag during adjustment, is described. The conjunctiva can be fully closed over the knot after adjustment, providing increased patient comfort and a better cosmetic result.

Personality and theophylline pharmacokinetics.

Thirteen volunteers received an iv dose of theophylline followed by blood sampling for 8 h to calculate pharmacokinetic parameters. Ten patients with asthma undergoing chronic dosing with slow release aminophylline underwent 12 h of blood sampling to calculate theophylline clearance. Both groups completed an Eysenck Personality Inventory (EPI) from which was derived scores for neuroticism (N) and extroversion (E). Using multiple regression analysis no independent effect of either N or E score on theophylline clearance or half-life could be demonstrated.

Anaphylactoid responses of two types of genetically different rats to horse serum and yeast.

Rats selectively bred for non-reactivity to clinical dextran (NR rats) fail to exhibit the anaphylactoid reaction to systemic baker's yeast or horse serum. Rats which respond with an anaphylactoid reaction to clinical dextran (R rats) react to baker's yeast but do not react to horse serum. The widespread oedema produced in R rats by systemic baker's yeast provides yet another clear method of differentiating them from NR rats.