The Concise Guide to PHARMACOLOGY 2013/14: overview.

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets. It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

River Pollution Diagnostic System (RPDS)--computer-based analysis and visualisation for bio-monitoring data.

The importance of biological monitoring for the assessment of river quality is well established. Bio-monitoring programmes, in particular the recording of benthic macroinvertebrate assemblages, produce an abundance of data to support the process of river quality assessment. However, current data analysis techniques are largely based on subjective score systems that do not fully realise the potential information value of such complex multivariate data sets. More advanced techniques of data analysis and visualisation can help to maximise the value of biological data, and hence to more efficiently and effectively direct resources, funding and research. A River Pollution Diagnostic System (RPDS) is described. RPDS was recently developed by the authors for the Environment Agency in England and Wales; it aims to maximise information retrieval from biological and environmental data.

Osteochondritis dissecans of the knee in children. A comparison of MRI and arthroscopic findings.

The treatment of osteochondritis dissecans (OCD) in children and adolescents is determined by the stability of the lesion and the state of the overlying cartilage. MRI has been advocated as an accurate way of assessing and staging such lesions. Our aim was to determine if MRI scans accurately predicted the subsequent arthroscopic findings in adolescents with OCD of the knee. Some authors have suggested that a high signal line behind a fragment on the T2-weighted image indicates the presence of synovial fluid and is a sign of an unstable lesion. More recent reports have suggested that this high signal line is due to the presence of vascular granulation tissue and may represent a healing reaction. We were able to improve the accuracy of MRI for staging the OCD lesion from 45% to 85% by interpreting the high signal T2 line as a predictor of instability only when it was accompanied by a breach in the cartilage on the T1-weighted image. We conclude that MRI can be used to stage OCD lesions accurately and that a high signal line behind the OCD fragment does not always indicate instability. We recommend the use of an MRI classification system which correlates with the arthroscopic findings.

Bizarre parosteal osteochondromatous proliferation with cortical invasion.

A 15-year-old male presented with an 18-month history of increasing swelling on the radial aspect of his left forearm. Radiographs and MR images showed a partly calcified mass on the lateral border of the radius with erosion of the underlying cortex. Following a CT-guided needle biopsy, the mass was excised by segmental resection of the radial shaft with replacement by a vascularised fibular graft. Histological examination of the resected specimen showed many features typical of a bizarre parosteal osteochondromatous proliferation (BPOP) but with destruction of the underlying cortical bone by cellular spindle cell tissue. Although there were no cytological signs of malignancy, we believe that this unusual disease should be regarded as a particularly aggressive form of BPOP and treated by wide excision. Clinical follow-up of our patient at 2 years shows no sign of local recurrence or metastasis.

Perioperative nurse training in cardiothoracic surgical robotics.

The exponential growth of OR technology during the past 10 years has placed increased demands on perioperative nurses. Proficiency is required not only in patient care but also in the understanding, operating, and troubleshooting of video systems, computers, and cutting edge medical devices. The formation of a surgical team dedicated to robotically assisted cardiac surgery requires careful selection, education, and hands-on practice. This article details the six-week training process undertaken at Sarasota Memorial Hospital, Sarasota, Fla, which enabled staff members to deliver excellent patient care with a high degree of confidence in themselves and the robotic technology.

MediCaring: development and test marketing of a supportive care benefit for older people.

OBJECTIVES: To develop an alternative healthcare benefit (called MediCaring) and to assess the preferences of older Medicare beneficiaries concerning this benefit, which emphasizes more home-based and supportive health care and discourages use of hospitalization and aggressive treatment. To evaluate the beneficiaries' ability to understand and make a choice regarding health insurance benefits; to measure their likelihood to change from traditional Medicare to the new MediCaring benefit; and to determine the short-term stability of that choice. DESIGN: Focus groups of persons aged 65+ and family members shaped the potential MediCaring benefit. A panel of 50 national experts critiqued three iterations of the benefit. The final version was test marketed by discussing it with 382 older people (men > or = 75 years and women > or = 80 years) in their homes. Telephone surveys a few days later, and again 1 month after the home interview, assessed the potential beneficiaries' understanding and preferences concerning MediCaring and the stability of their responses. SETTINGS: Focus groups were held in community settings in New Hampshire, Washington, DC, Cleveland, OH, and Columbia, SC. Test marketing occurred in New Hampshire, Cleveland, OH; Columbia, SC, and Los Angeles, CA. PARTICIPANTS: Focus group participants were persons more than 65 years old (11 focus groups), healthcare providers (9 focus groups), and family decision-makers (3 focus groups). Participants in the in-home informing (test marketing group) were persons older than 75 years who were identified through contact with a variety of services. MEASUREMENTS: Demographics, health characteristics, understanding, and preferences. RESULTS: Focus group beneficiaries between the ages of 65 and 74 generally wanted access to all possible medical treatment and saw MediCaring as a need of persons older than themselves. Those older than age 80 were mostly in favor of it. Test marketing participants understood the key points of the new benefit: 74% generally liked it, and 34% said they would take it now. Preferences were generally stable at 1 month. In multivariate regression, those preferring MediCaring were wealthier, more often white, more often living in senior housing, and using more homecare services. However, they were not more often in poor health or needing ADL assistance. CONCLUSIONS: Older persons aged more than 80 years can understand a health benefit choice; most liked the aims of a new supportive care benefit, and 34% would change immediately from Medicare to a supportive care benefit such as MediCaring,. These findings encourage further development of special programs of care, such as MediCaring, that prioritize comfort and support for the old old.

Endoscopic coronary artery bypass graft (ECABG) procedure with robotic assistance.

BACKGROUND: Technical details of the Robotically assisted endoscopic coronary artery bypass graft (ECABG) procedure on the cadaver model are reported. Moreover, this study will provide essential techniques, steps, and procedural development concepts necessary to introduce the ZEUS Robotic Surgical System (Computer Motion, Inc., Goleta, CA) into the human operating room. METHODS: Between August 1998 and March 1999, an ECABG procedure was performed on 10 cadaver torsos. The cadaver torso was placed in the left anterior oblique (LAO) position. The left and right internal mammary arteries (IMA) were taken down endoscopically. The ends of the IMA's were intracorporeally prepared. An upper partial sternotomy was demonstrated for perfusion cannulation and proximal anastomoses for multiple vessel revascularization. An arteriotomy was created with an endoscopic scalpel. The IMA was anastomosed to a chosen coronary using robotic assistance. The patency was verified by probing and injecting of methylene blue. RESULTS: Templates were developed to determine the placement of the robotic arms. Port templates were developed to both harvest the IMA's and perform the desired anastomoses. The following vessels were accessed through the developed port templates and retraction of the heart: left anterior descending (LAD), right coronary artery (RCA), diagonal (D(1)), obtuse marginal (OM(1) and OM(2)), and posterior descending artery (PDA). CONCLUSIONS: The use of robotic assistance during an ECABG procedure on a cadaver model is feasible. This study is a necessary and useful progression from the use of robotics in the animal lab to the use of robotics in the human operating room.

How opioids inhibit GABA-mediated neurotransmission.

The midbrain region periaqueductal grey (PAG) is rich in opioid receptors and endogenous opioids and is a major target of analgesic action in the central nervous system. It has been proposed that the analgesic effect of opioids on the PAG works by suppressing the inhibitory influence of the neurotransmitter GABA (gamma-aminobutyric acid) on neurons that form part of a descending antinociceptive pathway. Opioids inhibit GABA-mediated (GABAergic) synaptic transmission in the PAG and other brain regions by reducing the probability of presynaptic neurotransmitter release, but the mechanisms involved remain uncertain. Here we report that opioid inhibition of GABAergic synaptic currents in the PAG is controlled by a presynaptic voltage-dependent potassium conductance. Opioid receptors of the mu type in GABAergic presynaptic terminals are specifically coupled to this potassium conductance by a pathway involving phospholipase A2, arachidonic acid and 12-lipoxygenase. Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products. These mechanisms account for the analgesic action of cyclooxygenase inhibitors in the PAG and their synergism with opioids.

Do advance directives provide instructions that direct care? SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

OBJECTIVE: To evaluate whether the lack of effect of advance directives (ADs) on decision-making in SUPPORT might arise, in part, from the content of the actual documents. DESIGN: Advance directives placed in the medical records were abstracted for date of completion and content of additional written instructions. We examined directives with instructions to forgo life-sustaining treatment in the current state of health to determine whether care given was consistent with preferences noted in those directives. SETTINGS: Five teaching hospitals in the United States. PATIENTS: A total of 4804 patients with at least one of nine serious illnesses were admitted to five teaching hospitals in the 2 years following implementation of the Patient Self-Determination Act. Patients were part of a randomized controlled trial to improve decision-making and outcomes. RESULTS: From the medical records of 4804 patients, a total of 688 directives were collected from 569 patients. The majority of these directives (66%) were durable powers of attorney; in addition, 31% were standard living wills or other forms of written instructions (3%). Only 90 documents (13%) provided additional instructions for medical care beyond naming a proxy or stating the preferences of a standard living will. Only 36 contained specific instructions about the use of life-sustaining medical treatment, and only 22 of these directed forgoing life-sustaining treatment in the patient's current situation. For these, the treatment course was consistent with the instruction for nine patients. In two cases, patients may have changed an inconsistent directive after discussion with hospital staff. CONCLUSION: Advance directives placed in the medical records of seriously ill patients often did not guide medical decision-making beyond naming a healthcare proxy or documenting general preferences in a standard living will format. Even when specific instructions were present, care was potentially inconsistent in half of the cases.

Fetal maternal case management.

Multiple transfers, multiple specialists, and an unpredictable hospital course can result in ineffective communications among patients and the health care team. Complex care requirements easily become fragmented and lack coordination, thus overwhelming a family and even a well-intended multidisciplinary care delivery team. Because of this concern, the Greater Kansas City Fetal Board originated and implemented a new nursing case management model for high-risk obstetric and fetal patients. Fetal maternal case management crosses traditional hospital and provider boundaries with the pregnant patient. Case management allows parents to identify treatment options, and then create with specialists a plan of care. Case managers work with parents to identify support systems and explore parental preferences. The purpose of this article is to describe the fetal maternal case management model. Readers will better understand the need and value of such a program, as well as gain insight into how to facilitate fetal maternal case management.

delta-opioid receptor mobilization of intracellular calcium in SH-SY5Y cells: lack of evidence for delta-receptor subtypes.

delta-opioid receptor agonists mobilize intracellular Ca2+([Ca2+]i) in SH-SY5Y cells when applied in the presence of muscarinic agonists. The putative delta 1 receptor agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE) elevated [Ca2+]i with an EC50 of 11 nM and the putative delta 2 agonist deltorphin II elevated [Ca2+]i, with an EC50 of 14 nM. The maximal elevations of [Ca2+]i caused by both agonists were not different, nor were maximally effective concentrations of DPDPE (1 microM) and deltorphin II (1 microM) applied together more effective than either agonist applied alone. The elevations of [Ca2+]i caused by DPDPE (1 microM) and deltorphin II (1 microM), in the presence of carbachol, desensitized rapidly with continued opioid exposure and the cross-desensitization between PDPDE and deltorphin II was complete. The putative delta 1 selective antagonist 7-benzylidenenaltrexone (BNTX) and the putative delta 2 selective antagonist naltriben both reduced the elevations of [Ca2+]i caused by DPDPE (30 nM) and deltorphin II (10 nM), by greater than 50% at concentrations of less than 10 nM. In SH-SY5Y cells delta-receptor mediated elevation of [Ca2+]i is mediated by a population of receptors, which does not discriminate between agonists and antagonists purportedly selective for delta 1 or delta 2 receptors.

Retrospective self-reported symptoms of attention-deficit hyperactivity disorder: reliability of the Wender Utah Rating Scale.

We measured the internal consistency and four-week temporal consistency and temporal stability of the Wender Utah Rating Scale and its 25-item short form. The Wender scale is a rationally constructed retrospective self-report rating scale for symptoms of Attention-deficit Hyperactivity Disorder. Both scales manifested excellent internal consistency. Over one month, both versions manifested significant temporal consistency and good temporal stability in the nonclinical sample of 83 successful young adults most likely to be referred for an evaluation of suspected Attention-deficit Hyperactivity Disorder. The collegiate group had a considerably higher Wender score than the original normative group, calling into question the adequacy of the limited normative data. However, both forms of the scale are reliable and comprehensive validation research is advocated.

Laser operator training and competency assessment in the community hospital setting.

At the 279 bed Marymount community hospital, Cleveland, Ohio, the importance of providing a safe laser environment for patients as well as staff was identified. The decision was made to cross-train all full-time RNs, LPNs, and SAs to allow flexibility in staffing all laser procedures with a qualified operator. A competency based training program was implemented, utilizing a combination of techniques to assist the adult learner. Selected video tapes were used to teach laser physics and applications. Comprehension was assessed through written and oral quizzing. Individual time was spent familiarizing trainees with the equipment and accessories. Practice setups were performed until that individual reached a comfort level satisfactory to him/her and the laser coordinator. Actual experience in the various surgical specialties was dependent upon our case load. Initially very close supervision was provided. Each trainee was gradually given more autonomy as his/her skills improved and permitted to operate the laser independently after passing our competency assessment. During the first year, each operator was given competency assessment reviews at regular intervals. This approach was found to have both strengths and weaknesses and the program was modified accordingly.

MediCaring: comprehensive support services as a Medicare option.

MediCaring is a feasibility project that aims to develop an alternative benefit for comprehensive, supportive, home-based care to individuals who are enrolled in Medicare. Will Medicare-eligible consumers be willing to relinquish acute care benefits to finance supportive, home-based care?

Ionic zinc may function as an endogenous ligand for the haloperidol-sensitive sigma 2 receptor in rat brain.

In the search for an endogenous sigma transmitter, whose existence was previously suggested by release studies, we tested the effects of releasable substances known to be present in the hippocampus, and we determined that ionic zinc may function as an endogenous ligand for the haloperidol-sensitive sigma 2 site. Zn2+ displaced 1,3-di(2-[5-3H]tolyl)guanidine ([3H]DTG) from two binding sites in rat brain membranes, with an IC50 for the high affinity site of 110 +/- 3 microM and for the low affinity site of 20 +/- 4 mM. The sigma 1-selective ligand (+)-[3H]pentazocine was only weakly displaced from rat brain membranes by Zn2+ (IC50 = 1.4 +/- 0.05 mM). These results indicate that the Zn(2+)-sensitive sigma binding site corresponds to the sigma 2 site. The interaction between Zn2+ and the sigma 2 site may have physiological significance, because ionic zinc is present in synaptic vesicles in the brain and may function to regulate binding at the sigma 2 site. To test this hypothesis, we measured the effects of metallothionein peptide 1, a specific zinc chelator, on the actions of the putative endogenous sigma ligand(s) released in the hippocampus by focal electrical stimulation. Release of the endogenous sigma ligand(s) was measured by competition with specific radioligand binding in live hippocampal slices. High frequency, focal, electrical stimulation of the zinc-containing mossy fibers in the hilar region of the hippocampus caused a decrease in the specific binding of [3H]DTG, (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine, or (+)-[3H]pentazocine to sigma sites. The decrease in [3H]DTG binding was largely blocked by metallothionein peptide 1, whereas the decrease in (+)-[3H]pentazocine binding was unaffected. These results suggest that Zn2+ may act as an endogenous ligand at sigma 2 sites in the rat hippocampus.

Self-reported safety practices in child care facilities.

To determine the prevalence of safety hazards and current injury prevention practices in child care settings, we administered a structured telephone interview to a geographically stratified, randomly selected sample of licensed child care facilities. Representatives of 130 child care facilities responded to questions about current injury prevention practices. Specific hazards assessed were related to burns, falls, poisoning, playgrounds, and emergency telephone numbers. Results indicated that 26.8% of providers who knew the temperature of their tap water stated that it was over 130 degrees F.; 14.1% had space heaters accessible to children; 30.3% of those with stairs accessible to children lacked safety gates; 61.4% of those with playgrounds did not have an impact-absorbing surface under playground equipment; 16.9% of respondents had an unexpired bottle of syrup of ipecac; 55.8% demonstrated that a poison control center telephone number was available to them; and 80% of providers could demonstrate the availability of the telephone number of the local ambulance. We conclude that potential and remedial injury hazards exist in some licensed child care centers and that providers of child care within licensed facilities are a promising target for childhood injury prevention interventions.

Focal stimulation of specific pathways in the rat hippocampus causes a reduction in radioligand binding to the haloperidol-sensitive sigma receptor.

Focal electrical stimulation of selected excitatory pathways in the hippocampal slice caused a decrease in the binding of [3H]-1,3-di(2-tolyl)guanidine (DTG) or [3H]-(+)-3-[hydroxyphenyl]-N-(1-propyl)piperidine [( 3H )-(+)3-PPP) to haloperidol-sensitive sigma binding sites in the slice. Activation of the mossy fibers or perforant path by high frequency electrical stimulation caused the reduction in [3H]-DTG binding; whereas activation of fibers in the strata radiatum, lacunosum-moleculare, alveus, or oriens did not affect [3H]-DTG binding. The decrease in binding observed was calcium-dependent and tetrodotoxin sensitive and varied with the frequency, intensity, and duration of stimulation. Although haloperidol-sensitive [3H]-DTG binding sites are distributed throughout the hippocampus, stimulation of the perforant path or mossy fibers resulted in a significant reduction in binding only in the dentate region of the slice. The decrease in binding following perforant path stimulation was blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); whereas the decrease in binding caused by mossy fiber stimulation was not affected by CNQX or DL-APV. The results obtained support the hypothesis that activation of the granule cells in the hippocampal slice caused the release of an endogenous ligand which acts at the haloperidol-sensitive sigma binding site in the dentate gyrus.