Unconscious incompetence and the foundation years.
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Clinical Competence↗
Biomedical subjects
A Hicks
Publications and source records attributed to A Hicks.
Which way ahead?: I want my doctor to.... The mechanics of market research for medics in the millenium: special communication.
A brief description is given of the changing politico-social structure today involving medicine and especially the cosy personal doctor-patient relationship of the past which has now become triangular involving Managed Health Care Organisations in many cases. The Medical Practitioners' and Dentists' Board (the Board) appointed the Ethics Conference Committee largely composed of non-Board members to collect and collate information of what doctors, paramedics and the lay public expected from their doctors today. It is planned that the Committee's Report summarising this information would form the basis of the new guidelines to modern ethics to be published by the Board later. In this paper the mechanics, funding and production of the report are described but not the contents of the report which is still being considered by the new Board.
Attitude of Health Personnel↗
Identification of medication-related attendances at an A & E department.
BACKGROUND: The use of medication is the most common medical intervention, but it has associated risks. These have been described as drug-related problems (DRPs). Other non-UK studies have reported DRPs to be the cause of 3-16% of hospital admissions and around 4% of attendances at emergency departments. The size of the problem in the UK has not been quantified. AIM: The aim of this study was to identify the number of patients attending a central London accident and emergency (A & E) department with symptoms or conditions caused by DRPs. METHOD: A 2-week retrospective, case-review study was conducted in the A & E department of St Thomas' Hospital, London, during March 1999. DRPs were identified using recognized criteria. Statistical analysis identified patient characteristics which could be associated with the incidence of DRPs. The types of DRP and the drugs involved were identified. RESULTS: During the study period, 106 patients attended the A & E department with a DRP. This equates to 4% of the A & E population. During this period the demographics of the A & E attenders were no different to the annual A & E cohort. The most common DRPs were adverse drug reactions and overdose. The most frequently involved drugs included analgesics, antibiotics, those with narrow therapeutic indices and illegal drugs. The mean age of this patient group was 38 years (non-significant). They attended significantly more frequently during the early hours of the morning and on Saturdays than the A & E general population (chi-squared P = 0.004 and P = 0.003, respectively). DISCUSSION: The incidence of DRP as a cause of attendance at A & E reflects that in the literature. No statistical association with a specific age group of patients could be made, but the mean age of 38 years is younger than previously reported. The demographic differences which were statistically significant can be explained by the increased incidence of DRP associated with the use of illegal drugs than reported in other studies. Other drug groups identified by this study are representative of other reports. CONCLUSION: DRPs account for 4% of attendances at a central London A & E Department.
Adult↗
Inhibitory and enhancing effects of IFN-gamma and IL-4 on SHIV(KU) replication in rhesus macaque macrophages: correlation between Th2 cytokines and productive infection in tissue macrophages during late-stage infection.
HIV-1 is dual-tropic for CD4+ T lymphocytes and macrophages, but virus production in the macrophages becomes manifest only during late-stage infection, after CD4+ T cell functions are lost, and when opportunistic pathogens begin to flourish. In this study, the SHIV/macaque model of HIV pathogenesis was used to assess the role of cytokines in regulating virus replication in the two cell types. We injected complete Freund's adjuvant (CFA) intradermally into SHIV(KU)-infected macaques, and infused Schistosoma mansoni eggs into the liver and lungs of others. Tissues examined from these animals demonstrated that macrophages induced by CFA did not support viral replication while those induced by S. mansoni eggs had evidence of productive infection. RT-PCR analysis showed that both Th1 (IL-2 and IFN-gamma) and Th2 cytokines (IL-4 and IL-10) were present in the CFA lesions but only the Th2 cytokines were found in the S. mansoni lesions. Follow-up studies in macaque cell cultures showed that whereas IFN-gamma caused enhancement of virus replication in CD4+ T cells, it curtailed viral replication in infected macrophages. In contrast, IL-4 enhanced viral replication in infected macrophages. These studies strongly suggest that cytokines regulate the sequential phases of HIV replication in CD4 T cells and macrophages.
Animals↗
Developments in education and training for nursing home staff.
The independent sector has always provided a proportion of the care needed for a variety of client groups in the UK. Although the vast majority of the recipients of care are older people, groups such as those with mental health problems and those suffering from various disabilities are also cared for. The sector is currently facing the need for major changes in the way it provides care. Legislation and a number of reports and strategy documents mean that these changes are necessary for the sector to survive. To drive and to respond to the new situation, education and training has a part to play. This article will examine how the new situation following the sector will impact on the education needs for nurses.
Aged↗
Tissue oxygenation by near-infrared spectroscopy and muscle blood flow during isometric contractions of the forearm.
The relationship between tissue oxygenation measured by near-infrared spectroscopy (NIRS) and forearm muscle blood flow (FBF) measured by Doppler ultrasound was tested during isometric contractions at 10 and 30% maximal voluntary contraction (MVC) under conditions of normoxia and hypoxia (14% inspired O2). Six subjects maintained contractions at 10% MVC for 5 min and 30% for 2 min in both gas conditions. FBF was elevated during exercise at 10% MVC in hypoxia compared to normoxia, but there was no further increase in flow at 30% MVC. Median power frequency calculations from electromyographic recordings suggested progressive development of fatigue throughout both 10 and 30% MVC contractions. NIRS indicated no change in muscle oxygenation at 10% MVC, but deep venous blood O2 saturation was reduced in normoxia and more so in hypoxia. At 30% MVC, both NIRS and venous O2 saturation were reduced, with no effect of hypoxia on the NIRS signal. While NIRS might provide an indication of muscle oxygenation during isometric exercise, the conflicting findings for NIRS and direct venous blood sampling at 10 vs 30% MVC suggest caution in the application of this noninvasive technique.
Adult↗
The optimal joint angle for adductor pollicis force production in men and women.
The purpose of this study was to determine the joint angle that allows for the greatest MVC and evoked twitch forces from the adductor pollicis (AP), and also whether there is a gender difference in either the above forces or the optimum thumb angle. Ten men (25.2 yrs) and 10 women (27.6 yrs) participated. The nondominant hand was placed palm-down with the thumb fixed at four angles of abduction (55, 70, 85, 100 degrees). Male MVC forces were significantly greater than female, and there was no significant effect of joint angle on MVC force in either gender. For the evoked twitch, men were significantly stronger than women when tested at the 100 and 85 degrees angles, and a significant effect was found for joint angle such that the lowest twitch force occurred at 55 degrees. Men also tended to have a greater rate of force development than women (p = 0.07). These data suggest that studies using the AP muscle in stimulated and voluntary paradigms should use a thumb angle between 70 and 100 degrees of abduction, or approximately 85 degrees, and that the same angle can be used for both men and women.
Adult↗
The effect of beta-blockade on plasma potassium concentrations and muscle excitability following static exercise.
The effects of beta-blockade on plasma [K+], muscle excitability and force during fatiguing exercise were examined. Nine healthy males (mean age 22.3+/-1.7 yr) performed a 3-min fatigue protocol that consisted of a sustained submaximal contraction (30% of the maximal voluntary contraction, MVC) of the right quadriceps muscle. Subjects performed the exercise after treatment with either placebo, beta1-selective (metoprolol, 100 mg) or an equipotent dose of non-selective beta1,2-blockade (propranolol, 80 mg, n=6; 100 mg, n=2; 120 mg, n=1) twice daily for 3 days before testing according to a randomized double-blind design. Brachial arterial and femoral venous blood samples were drawn before, during, and for 15 min following the contraction, together with maximal stimulation of the right femoral nerve to evoke a twitch and a compound muscle action potential (M-wave); the M-wave amplitude being used as an index of sarcolemmal excitability. The exercise-induced rise in plasma [K+] did not differ between treatments, but K+ re-uptake during recovery was slower following propranolol. The recovery of the twitch was significantly related to the recovery of plasma [K+] in all trials, but the evoked M-waves were unaffected by either the contraction or the drug treatment. Propranolol resulted in a significantly (P<0.05) greater reduction (51.9+/-7.3%) in MVC following the 3-min contraction compared with metoprolol (40.7+/-3.6%) or placebo (38. 9+/-3.6%). These results suggest that while beta1,2-blockade may significantly affect the recovery of muscle force and K+ homeostasis after fatiguing exercise (presumably through an inhibition of the Na+,K+-ATPase), it does not appear to affect surface membrane excitability.
Action Potentials↗
Becoming ADEPT (Applying Diagnosis, Etiology, Prognosis, and Therapy Programme): delivering distance learning on evidence-based medicine for librarians.
Evidence-based medicine (EBM) brings new challenges and opportunities for librarians. However, their ability to respond to this agenda is constrained by their difficulties in acquiring the requisite new skills and techniques while continuing to work in a busy information practice setting. The authors describe a joint initiative, between a specialist evidence-based healthcare information unit and a regional library network, to deliver training materials using a mixed workshop and distance learning format. The Applying Diagnosis, Etiology, Prognosis, and Therapy filters (ADEPT) Programme draws upon research conducted at McMaster University, Canada and, using techniques adapted from the teaching evidence-based medicine paradigm, seeks to equip health care librarians with the skills and techniques required to support evidence-based practice locally. The authors describe the thinking behind the programme, its main features, the extensive evaluation mechanisms incorporated into the course, the results of the evaluation and the lessons learnt. They conclude with a description of the way forward for participants on the programme who are adapting their newly acquired knowledge to their work situations. Further planned developments from the course's designers are also outlined briefly.
Cooperative Behavior↗
Increase in syntaxin 1B and glutamate release in mossy fibre terminals following induction of LTP in the dentate gyrus: a candidate molecular mechanism underlying transsynaptic plasticity.
A growing body of evidence suggests that modulation of certain proteins of the exocytotic machinery is, in part, involved in the biochemical changes that underlie long-term synaptic plasticity. We have previously shown that the induction of long-term potentiation (LTP) at perforant path to dentate granule cell synapses in the rat hippocampus induces changes in the mRNA levels of syntaxin 1B and synapsin I, known to be involved in neurotransmitter release. Immunohistochemical staining suggested that concomitant changes in these proteins occurred at mossy fibre synapses, downstream of those synapses at which LTP was induced, leading us to postulate that such a mechanism might underlie a form of transsynaptic plasticity. Here we have used a specific mossy-fibre synaptosome preparation to quantify levels of proteins and measure, using a chemiluminescent glutamate assay, depolarization-induced glutamate release from these synaptosomes after induction of LTP in the dentate gyrus in vivo. We show that 5 h after the induction of LTP, there is an increase in the protein levels of syntaxin 1B and, although to a lesser extent, the synapsins I and II, associated with an increase in depolarization-induced release of glutamate within these terminals. Increases in both the protein levels and glutamate release were not observed when dentate gyrus LTP was blocked by an NMDA receptor antagonist. From these results we propose a molecular mechanism for the propagation of synaptic plasticity through hippocampal circuits.
Animals↗
Induction of long-term potentiation in vivo regulates alternate splicing to alter syntaxin 3 isoform expression in rat dentate gyrus.
The regulation and specificity of the interactions between the proteins involved in neurotransmitter release are obvious targets for the cellular control of synaptic plasticity. Previous research has identified one of these proteins, syntaxin 1B, as a potential target for mediating the propagation of synaptic plasticity through neural networks. The expression of syntaxin 1B is modified in the hippocampus after the induction of long-term potentiation (LTP) and during learning. Here, we describe the identification of two other members of the syntaxin family from rat brain, syntaxins 3A and 3B, and show that they are generated from the same gene by alternate splicing. In situ hybridization and immunohistochemical staining confirm the expression of syntaxins 3A and 3B in the adult rat brain. The transcripts and proteins show a lower abundance but a similar pattern of expression as syntaxins 1A and 1 B. By using quantitative competitive PCR, we show that the mRNAs that encode syntaxins 1B and 3A are increased in dentate granule cells 6 h after the induction of LTP in vivo, whereas syntaxin 3B mRNA is decreased as rapidly as 30 min, and lasts for at least 6 h, after the induction of LTP. These findings identify coordinated changes in the expression of several syntaxin isoforms with different substrate specificities and suggest that regulation of the splicing machinery by LTP induction is one of the diverse strategies used during the long-term modification of the synapse in the vertebrate nervous system.
Alternative Splicing↗
Safety in acupuncture. Core curriculum is important.
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Acupuncture Therapy↗
Synapsin I and syntaxin 1B: key elements in the control of neurotransmitter release are regulated by neuronal activation and long-term potentiation in vivo.
The messenger RNAs encoding proteins of the exocytotic machinery were measured at different times following the induction of long-term potentiation or increasing neuronal activity in the dentate gyrus of the rat in vivo. In situ hybridization revealed that from the many messenger RNAs that encode proteins involved in regulated exocytosis, only those encoding synapsin I and syntaxin 1B were specifically increased. The levels of messenger RNA encoding both synapsin I and syntaxin 1B were increased on the ipsilateral side of the dorsal dentate gyrus 2 and 5 h following the induction of long-term potentiation. Syntaxin 1B was also increased in the ventral dentate gyrus at the same time-points. On the contralateral side of the dentate gyrus there was an increase in both synapsin I and syntaxin 1B at 5 h only. All of these long-term potentiation-induced changes were prevented when the tetanus was delivered in the presence of the N-methyl-D-aspartate receptor antagonist. (D(-)-2-amino-5-phosphonopentanoic acid. Immunocytochemical staining revealed that protein levels for both synapsin I and syntaxin 1B were elevated in the mossy fibre terminal zone of CA3 5 h after the induction of long-term potentiation. In addition to these plasticity-induced changes, a transient increase in the messenger RNA encoding syntaxin 1B was observed at 2 h in conditions of high intensity stimulation of the perforant path to increase the level of cellular activation, but this change was not maintained even when high intensity stimulation was sustained for 5 h. No changes in either of the messenger RNAs were observed under low frequency stimulation and pseudotetanus at either time-points. These results show that an overall increase in neuronal excitation within a neuronal network can be differentiated from a change in synaptic strength at a specific subset of the synapses, where only synaptic plasticity leads to long-term changes in the expression of selective members of the exocytotic machinery. Altered concentrations of key vesicle proteins may thus provide the means for modulation of neurotransmitter release over long time-periods. The persistent long-term potentiation-induced postsynaptic increase in messenger RNAs encoding these presynaptic proteins has important implications for the propagation of signals downstream from the site of long-term potentiation induction in hippocampal neural networks, and highlights a candidate molecular mechanism for mediating the propagation of synaptic plasticity in such networks.
Animals↗
Early functional and biochemical adaptations to low-frequency stimulation of rabbit fast-twitch muscle.
To examine mechanisms underlying force reduction after the onset of chronic low-frequency (10 Hz) stimulation (CLFS), we exposed rabbit tibialis anterior muscles to various durations of CLFS. To follow changes in isometric contractile properties and electromyographic (EMG) activity, we studied stimulated and contralateral muscles during a terminal test at 10 Hz for 10 min. In addition, activities and protein amounts of the sarcoplasmic reticulum Ca(2+)-ATPase, content of Na(+)-K(+)-ATPase, and expression patterns of triad junction components were examined. Force output and EMG amplitude declined abruptly soon after the onset of stimulation, suggesting refractoriness of a large fiber population. Although twitch force and to a lesser extent EMG activity gradually recovered after stimulation for 6 days and longer, the muscles exhibited profoundly altered properties, i.e., enhanced fatigue resistance, absence of twitch potentiation, and prolonged contraction and relaxation times. These changes were associated with significant increases in Na(+)-K(+)-ATPase concentration and significant decreases in Ca(2+)-ATPase, ryanodine receptor, dihydropyridine receptor, and triadin concentrations over the course of the 20 days of stimulation. Alterations in excitability, Ca2+ handling, and excitation-contraction coupling prior to changes in myofibrillar protein isoforms may thus be responsible for early functional alterations.
Acclimatization↗
A gene map of the human genome.
The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.
Amino Acid Sequence↗
The effects of lithium on muscle contractile function in humans.
A side effect of lithium (Li+) treatment is fatigue. Li+ decreases inositol triphosphate (IP3) accumulation and IP3 may play a role in excitation-contraction (E-C) coupling in skeletal muscle. Li+ carbonate (600 mg b.i.d. x 6 days) was administered in a randomized, double-blind fashion to 12 males to measure the effect upon muscle contractile function: peak twitch torque (PTT), time to PTT, half-relaxation time, maximal voluntary contraction strength (MVC), percent motor unit activation, M-wave characteristics, and tetanic torque (3 min at 15 and 50 Hz). Li+ resulted in a significant decrease in 15- and 50Hz tetanic torque (P<0.00l), MVC, and resting PTT (P<0.05). There were no effects of Li+ upon any of the other measured variables. Li+ had a negative effect upon E-C coupling and did not affect central motor unit recruitment. Elucidation of the role of IP3 in E-C coupling may help to understand fatigue in some neuromuscular disorders.
Adult↗
The relationship between plasma potassium, muscle membrane excitability and force following quadriceps fatigue.
To examine the simultaneous changes in plasma [K+], muscle excitability and force during fatigue, ten male adults (mean age = 22 +/- 0.5 years) held an isometric contraction of their right quadriceps muscle at an intensity of 30% maximum voluntary contraction (MVC) for 3 min. Femoral venous and brachial arterial [K+] were determined from serial samples drawn before, during, and for 15 min following the 3-min contraction. Each blood sample was synchronized with a maximal stimulation of the right femoral nerve to evoke a twitch and compound muscle action potential (M-wave). Immediately post-exercise, twitch torque was only 42% of baseline and femoral venous plasma [K+] had increased significantly from 4.02 +/- 0.08 mmol/l to 5.9 +/- 0.22 mmol/l. Femoral venous plasma lactate rose to a peak level of 10.0 +/- 0.8 mmol/l at 1 min post exercise. The recovery of the twitch torque was exponentially related to the recovery of femoral venous plasma [K+] (r2 = 0.93, P < 0.01). There was no evidence for any loss of muscle membrane excitability during the period of increased extracellular [K+], in fact, the M-waves tended to be potentiated in the early phases of the recovery period. These results suggest that muscle membrane excitability is maintained in spite of increased extracellular [K+] following fatigue induced by a sustained submaximal quadriceps contraction. However, the strong relationship between twitch torque and femoral venous plasma [K+] suggests that K+ may be exerting its effect distal to surface membrane action potential propagation, most likely in the T-tubular region.
Adult↗
Brain structure and task-specific increase in expression of the gene encoding syntaxin 1B during learning in the rat: a potential molecular marker for learning-induced synaptic plasticity in neural networks.
The mRNAs encoding the synaptic vesicle proteins syntaxin 1B and synapsin I were measured using in situ hybridization in several brain regions--the dentate gyrus, CA3 and CA1 of the hippocampus, the parietal, the motor and prefrontal cortices and the core and shell of the accumbens--of rats that were learning a spatial reference or working memory task on a radial arm maze. The mRNA encoding syntaxin 1B was significantly increased in all hippocampal regions in rats learning the working memory task, whereas it was increased in the prelimbic area of the prefrontal cortex and the shell of the accumbens in rats learning the spatial reference memory task. No change in mRNA encoding syntaxin 1B was observed in the motor and parietal and cortices or the core of the accumbens, and the mRNA encoding synapsin I was not significantly different from that of naive caged controls or rats running the maze for continuous reinforcement in any of the brain structures examined. These results demonstrate that the gene encoding a key member of synaptic vesicle function is up-regulated in a task- and brain-specific manner during learning. They are discussed in terms of the potential role this protein may play in trans-synaptic propagation of plasticity within specific neural networks as a function of the information required in the laying down of different types of memory.
Animals↗