Ultrasound-guided approach to nerves (direct vs. tangential) and the incidence of intraneural injection: a cadaveric study.

This study evaluated the incidence of nerve puncture and intraneural injection based on the needle approach to the nerve (direct vs. tangential). Two expert operators in regional anaesthesia performed in-plane ultrasound-guided nerve blocks (n = 158) at different levels of the brachial plexus in cadavers, aiming either directly for the nerve (n = 77) or tangentially inferior to the nerve (n = 81). After reaching the outer limit of the nerve, the needle was intentionally advanced approximately 1 mm in both approaches, and 0.2-0.5 ml of saline was injected. Each operator classified (in real time) the needle tip and injectate as intraneural or not. Video clips showing the final position of the needle and the injection were evaluated in the same manner by seven independent expert observers who were blinded to the aims of this study. In addition, 20 injections were performed with ink for histological evaluation. Intraneural injections of saline were observed by the operator in 58% (45/77) of cases using the direct approach and 12% (10/81) of cases using the tangential approach (p < 0.001). The independent observers agreed with the operator in a substantial number of cases (Cohen's kappa index 0.65). Histological studies showed intraneural spread in 83% (5/6) of cases using the direct approach and in 14% (2/14) of cases using the tangential approach (p = 0.007). No intrafascicular injections were observed. There was good agreement between the operators' assessment and subsequent histological evaluation (Cohen's kappa = 0.89). Simulation of an unintentional/accidental advancement of the needle 'beyond the edge' of the nerve suggests significantly increased risk of epineural perforation and intraneural injection when a direct approach to the nerve is used, compared with a tangential approach.

Astronomy. ASASSN-15lh: A highly super-luminous supernova.

We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu ,AB = -23.5 ± 0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10(45) ergs s(-1), which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10(52) ergs, challenging the magnetar model for its engine.

Saved by focused echo evaluation in resuscitation.

A 74-year-old woman received thrombolysis for pericarditis. She subsequently developed shock and cardiac arrest. The case report describes the events of how a simple immediate bedside focused echo proved to be a life saving assessment. Current availability and training issues in focused transthoracic echo are discussed.

Saved by focused echo evaluation in resuscitation.

A 74-year-old woman received thrombolysis for pericarditis. She subsequently developed shock and cardiac arrest. The case report describes the events of how a simple immediate bedside focused echo proved to be a life saving assessment. Current availability and training issues in focused transthoracic echo are discussed.

Ultrasound in regional anaesthesia.

Ultrasound guidance is rapidly becoming the gold standard for regional anaesthesia. There is an ever growing weight of evidence, matched with improving technology, to show that the use of ultrasound has significant benefits over conventional techniques, such as nerve stimulation and loss of resistance. The improved safety and efficacy that ultrasound brings to regional anaesthesia will help promote its use and realise the benefits that regional anaesthesia has over general anaesthesia, such as decreased morbidity and mortality, superior postoperative analgesia, cost-effectiveness, decreased postoperative complications and an improved postoperative course. In this review we consider the evidence behind the improved safety and efficacy of ultrasound-guided regional anaesthesia, before discussing its use in pain medicine, paediatrics and in the facilitation of neuraxial blockade. The Achilles' heel of ultrasound-guided regional anaesthesia is that anaesthetists are far more familiar with providing general anaesthesia, which in most cases requires skills that are achieved faster and more reliably. To this ends we go on to provide practical advice on ultrasound-guided techniques and the introduction of ultrasound into a department.

Mineralised tissues as nanomaterials: analysis by atomic force microscopy.

Mineralised tissues, such as bone, consist of two material phases: collagen protein fibrils that form the structural models upon which the mineral, calcium hydroxyapatite, is subsequently deposited. Collagen and mineral are removed in a three-dimensional manner by osteoclasts during bone turnover in skeletal growth or repair, and matrix proteins are replaced by the synthetic activity of osteoblasts and then calcify. The resolution of atomic force microscopy and use of unmodified, fully calcified samples has enabled the imaging of the overall bone and dentine structure, including collagen and mineral phases. Mineral crystals, in the diameter size range of 225 nm up to 1.4 microm, were found in unmodified bone and dentine respectively. D-banded collagen is observed in dentine after acid treatment and in bone after osteoclast-mediated matrix resorption; axial periodicity values of approximately 67 and 69 nm are observed, respectively. These experimental approaches have enabled the structure of mineralised tissues to be examined in native samples and will facilitate the study of bone structure in important clinical disorders of the skeleton, such as osteoporosis.

Recapitulation of the parathyroid hormone-related peptide-Indian hedgehog pathway in the regenerating deer antler.

Parathyroid hormone (PTH)-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR) play an essential role in controlling growth plate development. The aim of the present study was to use the deer antler as a model to determine whether PTHrP and PPR may also have a function in regulating cartilage and bone regeneration in an adult mammal. Antlers are the only mammalian appendages that are able to undergo repeated cycles of regeneration, and their growth from a blastema involves a modified endochondral process. Immunohistochemistry was used to establish sites of localization of PTHrP and PPR in antlers at different stages of development. The pattern of Indian Hedgehog (IHH) and transforming growth factor-beta1 (TGF beta1) distribution was also investigated, because PTHrP expression in the developing limb is regulated by IHH and during embryonic growth plate formation TGF beta1 acts upstream of PTHrP to regulate the rate of chondrocyte differentiation. In the antler blastema (<10 days of development), PTHrP, PPR, and TGF beta1 were localized in epidermis, dermis, regenerating epithelium, and in mesenchymal cells but IHH expression was not detected. In the rapidly growing antler (weeks 4-8 of development), PTHrP, PPR, and TGF beta1 were localized in skin, perichondrium, undifferentiated mesenchyme, recently differentiated chondrocytes, and in perivascular cells in cartilage but not in fully differentiated hyperytrophic chondrocytes. IHH was restricted to recently differentiated chondrocytes and to perivascular cells in cartilage. In mineralized cartilage and bone, PTHrP, PPR, IHH, and TGF beta1 were immunolocalized in perivascular cells and differentiated osteoblasts. PTHrP and PPR were also present in the periosteum. TGF beta1 in vitro stimulated PTHrP synthesis by cells from blastema, perichondrium, and cartilage. The findings of this study suggest that molecules which regulate embryonic skeletal development and postnatal epiphyseal growth may also control blastema formation, chondrogenesis, and bone formation in the regenerating deer antler. This finding is further evidence that developmental signaling pathways are recapitulated during adult mammalian bone regeneration.

Reactive pocket epithelium in untreated chronic periodontal disease: possible derivation from developmental remnants of the enamel organ and root sheath.

The pathological lining epithelium of destructive periodontitis was studied by analysis of the expression of intermediate filament proteins in biopsies of untreated advanced periodontitis. The cytokeratin (CK) pair 8/18 characteristic of simple epithelia was expressed consistently in a distribution pattern confined to the reactive pocket epithelium. The pattern of CK8/18 expression was complex with two broad presentations evident. In two-thirds of the advanced disease biopsies, the entire pathological lining epithelium was strongly reactive for both CK8 and CK18. In the remainder, the more superficial lining epithelium was mixed with foci of reactive and unreactive cells, with the deeper epithelium uniformly reactive. Only occasional highly localised reactivity for the simple keratins (CK8/18) was found in the lining epithelia of biopsies from minimally inflamed periodontal tissues. The pathological lining epithelium of advanced periodontitis was further characterised by the co-expression in basal layers of CK14, and of CK13 but not CK4, which are characteristic of suprabasal layers of stratified squamous epithelia. Cytokeratin 17, a marker of high turnover and migrating epithelial cells was extremely variable with no clear association between expression pattern and location of the epithelium ordisease status. There was no reactivity for CK10/11 typical of cornifying cells nor of vimentin, the characteristic intermediate filament of mesenchymal cells. The intermediate filament protein profile of the reactive lining epithelium was indistinguishable from the reactive epithelium present in three of five biopsies of periapical granulomas containing hyperplastic epithelium from activation of the developmental remnants of Hertwig's sheath, known as the cell rests of Malassez. The data reported are compatible with a contribution by remnants of developmental epithelium, including the reduced enamel epithelium and the cell rests of Malassez, to the reactive lining epithelium of the subgingival pocket in the pathogenesis of chronic periodontitis.

Clinical pharmacokinetics of ropinirole.

Ropinirole is a selective non-ergoline dopamine D2 receptor agonist indicated for use in treating Parkinson's disease. When taken as oral tablets, ropinirole is rapidly and almost completely absorbed, and it is extensively distributed from the vascular compartment. The bioavailability is approximately 50%. Ropinirole shows low plasma protein binding. The drug is inactivated by metabolism in the liver, and none of the major circulating metabolites have pharmacological activity. The principal metabolic enzyme is the cytochrome P450 (CYP) isoenzyme CYP1A2. Ropinirole shows approximately linear pharmacokinetics when given as single or repeated doses, and is eliminated with a half-life of approximately 6 hours. Population pharmacokinetics have demonstrated that gender, mild or moderate renal impairment, Parkinson's disease stage and concomitant illnesses or the use of several common concomitant medications have no effect on the pharmacokinetics of ropinirole. Clearance is slower for patients older than 65 years compared with those who are younger, and in women taking hormone replacement therapy compared with those who are not. The CYP1A2 inhibitor ciprofloxacin produced increases in the plasma concentrations of ropinirole when these 2 drugs were coadministered, but no interaction was seen with theophylline which, like ropinirole, is also a substrate for CYP1A2. There is no obvious plasma concentration-effect relationship for ropinirole.

The effect of experimental epilepsy induced by injection of tetanus toxin into the amygdala of the rat on eating behaviour and response to novelty.

A minute dose of tetanus toxin injected into the amygdala of rats produced an apparently reversible epileptiform syndrome similar to that previously described after injection of the toxin into the hippocampus. During the active epilepsy the toxin-injected rats occasionally exhibited 'paroxysmal eating' and also sometimes ran round in circles attempting to bite their own tails. When presented with a novel but palatable food (chocolate buttons or harvest crunch) the toxin-injected rats showed less neophobia than their controls--they ate sooner and ate more. This was found both during the active epilepsy and several weeks later when they had recovered. A similar effect of amygdala injections was found in a second experiment, in which the effect was compared with that of toxin injection in the hippocampus. These rats were tested also on the playground maze on their approach response to a neutral novel object (in a familiar environment in the context of seven familiar objects). The amygdala rats did not show any increase in their novelty response; thus their reduction in neophobia was specific to an appetitive behaviour. In contrast, the hippocampally-injected rats did not exhibit a novelty response in the playground maze, but showed normal neophobia to a new food.

Heterogeneity in systemic availability of ondansetron and granisetron following oral administration.

This open-label, randomized, two-way crossover study compared the relative heterogeneity in systemic availability of oral ondansetron and granisetron. It was conducted in 10 healthy male and 10 healthy female subjects aged 18 to 50 years. Following an overnight fast, each subject received 8 mg ondansetron and 1 mg granisetron. Treatments were separated by 7 days. Blood samples for drug assay were collected over a period of 36 h and variability in pharmacokinetic parameter estimates were assessed following standardization by their respective means. Granisetron showed significantly more variability than ondansetron in the three primary endpoints of the area under the curve extrapolated to infinite time, the area under the curve to the last quantifiable time point, and maximal concentration (p =.0032,.0037, and.0042, respectively). In one subject, concentrations of granisetron were detectable but below the lower limit of quantitation at any time point. The impact this variability may have on therapeutic efficacy is not clear. An apparent bimodal distribution in granisetron AUC infinite, which appeared to be related to smoking was observed. Because granisetron has been reported to be metabolized primarily by the cytochrome P-450 (CYP) 3A isozyme family in humans, it is possible that cigarette smoke could be an inducer of CYP3A or that CYP1A2, also implicated in the metabolism of granisetron and known to be induced by smoking, is more important in the biotransformation of granisetron than previously thought.

The effect of Ro 15-4513, an inverse agonist at the benzodiazepine receptor, on the exploratory response to novelty in the playground maze.

The effects of chlordiazepoxide and the inverse agonist, Ro 15-4513, were compared on the exploratory response of rats to a novel object introduced into a familiar environment containing seven familiar objects. While chlordiazepoxide (5 mg/kg) increased the novelty response, Ro 15-4513 reduced the response in a dose-dependent manner (0.5-5.0 mg/kg). This action was specific to novelty since the response to the familiar objects was unaffected. Both drugs produced some reduction in ambulation. The effects of both drugs were blocked by flumazenil (10 mg/kg), which at this dose did not itself have any intrinsic effect on the response. Muscimol (0.001 mg/kg) had a weak chlordiazepoxide-like effect and baclofen (3 mg/kg) had a weak effect in the opposite direction.

The playground maze: a new method for measuring directed exploration in the rat.

A new test, called the 'playground maze', is described. Rat exploratory responses to a single novel object are measured in the context of responses to 7 familiar objects in a familiar environment. Responses are measured as time spent in areas around the objects on a circular open field. These times are expressed as percentages of the total time spent exploring all the objects and a value which is significantly greater than the expected chance level (12.5%) indicates a novelty response. The paths traversed by the animals on the maze are also recorded and the lengths of these give a measure of locomotion. Preliminary experiments on the effects of chlordiazepoxide (CDP) (1-5 mg/kg) and amphetamine (1.5-4 mg/kg) are reported. CDP significantly increased the novelty response but had no effect on locomotion. Amphetamine treatment at 4 mg/kg abolished the response to novel objects while lower doses (1.5 and 2 mg/kg) did not affect it. All 3 doses of amphetamine significantly increased locomotion. This test provides a new way of measuring the exploratory response to novelty under low stress conditions and allows the separation of drug effects on directed exploration and locomotion.