Osteomyelitis of the humerus complicating BCG vaccination.
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BCG Vaccine↗
Biomedical subjects
A Wainwright
Publications and source records attributed to A Wainwright.
Audit of a policy of magnetic resonance imaging with diffusion-weighted imaging as first-line neuroimaging for in-patients with clinically suspected acute stroke.
AIM: To audit the feasibility and use of diffusion-weighted (DW) magnetic resonance imaging (MRI) as initial neuroimaging for in-patients with clinically suspected acute stroke. MATERIALS AND METHODS: In April 2000, MRI with DW and T2-weighted sequence was locally instituted as initial neuroimaging for patients with clinically suspected acute stroke. This retrospective study reviewed imaging performed for in-patients with suspected acute stroke over a 9-month period. Data were collected on image type, result and need for repeat imaging. RESULTS: During the study period, 124 patients had neuroimaging for suspected cerebrovascular accident, and 119 were MRI safe. Eighty-eight (73.9%) patients underwent DW MRI as first-line investigation. Five patients were not MRI safe and 31 had computed tomography (CT) as first-line imaging due to lack of available MRI capacity. Repeat neuroimaging was performed in 16 (12.9%) patients. Study times were comparable for both types of neuroimaging: a mean of 13 min for MRI and 11 min for CT. CONCLUSION: The audit standard was achieved in 88 (73.9%) patients. The use of DW MRI as a first-line investigation for patients with a clinical diagnosis of acute stroke is achievable in a district general hospital setting.
Decision Making↗
Autoradiographic localization of (125)i[Tyr(14)] nociceptin/orphanin FQ binding sites in macaque primate CNS.
Nociceptin/orphanin FQ (N/OFQ) is a recently identified neuropeptide that has been implicated in a multitude of CNS functions. These include nociception, feeding, cognition, locomotion, stress and neuroendocrine control. The endogenous receptor for this ligand is the nociceptin/orphanin FQ peptide (NOP) receptor. The distribution of NOP in rodent has been widely reported by the use of in situ hybridization, immunohistochemistry and autoradiographic radioligand binding but less is known of its localization in higher species. We have therefore sought to optimize and determine the distribution of (125)I[Tyr(14)]N/OFQ binding sites in macaque primate brain and spinal cord. Highest levels of binding were observed in neocortical areas, hippocampus, amygdala, caudate nucleus and putamen, medial thalamic nuclei and superficial laminae of the superior colliculus. These novel data present for the first time, the distribution of N/OFQ receptors in non-human primate CNS and, by comparison with localization in the rat, reveal that species differences may exist in the distribution of this neuropeptide receptor. These data have important implications regarding the roles of N/OFQ across species and may have ramifications in the interpretation of preclinical pharmacological studies.
Animals↗
Distribution of 5-ht(5A), 5-ht(5B), 5-ht(6) and 5-HT(7) receptor mRNAs in the rat brain.
The precise involvement of 5-ht(5A), 5-ht(5B), 5-ht(6) and 5-HT(7) receptors in the pleiotropic actions of 5-HT remain incompletely known. To gain insights into their physiological function(s), localization of mRNAs encoding these subtypes was carried out using in situ hybridization on rat brain sections. Localization was heterogeneous. For example, 5-ht(5A) mRNA was widely expressed while 5-ht(5B) mRNA was predominantly expressed in habenula, hippocampus and inferior olive. 5-ht(6) mRNA was abundant in olfactory tubercles and caudate putamen, and highest levels of 5-HT(7) mRNA were observed in multiple thalamic nuclei. These data suggest that these receptors may have distinct functional roles within the serotonergic system.
Animals↗
Cloning, characterization and central nervous system distribution of receptor activity modifying proteins in the rat.
Calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), amylin and calcitonin (CT) are structurally and functionally related neuropeptides. It has recently been shown that the molecular pharmacology of CGRP and ADM is determined by coexpression of one of three receptor activity-modifying proteins (RAMPs) with calcitonin receptor-like receptor (CRLR). Furthermore, RAMP proteins have also been shown to govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. In this study, we have cloned the rat RAMP family and characterized the pharmacology of rat CGRP and ADM receptors. Rat RAMP1, RAMP2 and RAMP3 shared 72%, 69% and 85% homology with their respective human homologues. As expected CRLR-RAMP1 coexpression conferred sensitivity to CGRP, whilst association of RAMP2 or RAMP3 with CRLR conferred high affinity ADM binding. Using specific oligonucleotides we have determined the expression of RAMP1, RAMP2 and RAMP3 mRNAs in the rat central nervous system by in situ hybridization. The localization of RAMP mRNAs was heterogeneous. RAMP1 mRNA was predominantly expressed in cortex, caudate putamen and olfactory tubercles; RAMP2 mRNA was most abundant in hypothalamus; and RAMP3 was restrictively expressed in thalamic nuclei. Interestingly, in specific brain areas only a single RAMP mRNA was often detected, suggesting mutual exclusivity in expression. These data allow predictions to be made of where each RAMP protein may heterodimerize with its partner G-protein-coupled receptor(s) at the cellular level and consequently advance current understanding of cellular sites of action of CGRP, ADM, amylin and CT. Furthermore, these localization data suggest that the RAMP family may associate and modify the behaviour of other, as yet unidentified neurotransmitter receptors.
Adrenomedullin↗
A practical approach to the first iteration in the optimization of radiation dose and image quality in CT: estimates of the collective dose savings achieved.
CT is a diagnostic imaging modality giving higher patient dose in comparison with other radiological procedures. It contributed an estimated 20% to the collective effective dose to the UK population from medical X-rays in 1990, rising to an estimated 40% in 1999. Tremendous national effort has been expended in reducing patient doses from other radiological procedures with considerable success, but much of the collective dose reduction achieved has been offset by a corresponding increase in the collective dose from CT. Over a period of about 2 years, following the installation of a helical CT scanner, CT scan parameters in this hospital have been adjusted with the aim of working towards optimization of image quality and patient dose. A 33% reduction in annual collective effective dose has been achieved, from about 16.5 manSv to 11 manSv. However, despite this dose reduction, the annual collective effective dose to our sub-population is 2.8 times the value 9 years ago. The increase is almost entirely the result of an increased application of CT; 6149 examinations per annum in 1999 compared with 2210 in 1991. The crucial importance of reducing patient doses from this modality is discussed. Indicative effective doses and image noise values are presented for examination protocols approaching optimization.
Humans↗
Expression of GABA(A) receptor alpha5 subunit-like immunoreactivity in human hippocampus.
To investigate the distribution of GABA(A) receptor alpha5 subunit expression in brain, polyclonal antisera were raised, characterised and applied to human and rat brain sections. The resultant antibodies detected a major band of 53 kDa in sodium dodecyl sulphate-polyacrylamide gel electrophoresis immunoblots. Abundant immunostaining was demonstrated in the hippocampal formation in multiple cell types, although predominantly in pyramidal neurons. These data are supportive of GABA-ergic involvement in cognition, and suggest that this influence may be mediated through receptors containing the alpha5 subunit.
Animals↗
Localization of 5-ht(5A) receptor-like immunoreactivity in the rat brain.
5-Hydroxytryptamine exerts modulatory physiological effects on both the central and peripheral nervous systems by activation of discrete receptor families. 5-ht(5A) is among the recently cloned, novel 5-HT receptors and currently under investigation to identify its pharmacological characteristics and potential physiological function(s). In this study, antibodies raised to a 5-ht(5A)-specific peptide were characterized using dot blot, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunohistochemistry, and the distribution of 5-ht(5A)-like immunoreactive material determined in rat brain. A major band of 41 kDa was observed following SDS-PAGE, corresponding to the predicted size of this receptor. 5-ht(5A)-like immunoreactivity was detected in areas known to have significant serotonergic input, such as hypothalamic and amygdaloid nuclei. Interestingly, 5-ht(5A)-like immunoreactivity showed a predilection for the suprachiasmatic nucleus, suggesting its possible role in the regulation of circadian rhythms, a function previously ascribed to 5-HT(1A) and 5-HT(7) receptors.
Animals↗
Mobilisation of intracellular Ca2+ by mGluR5 metabotropic glutamate receptor activation in neonatal rat cultured dorsal root ganglia neurones.
The ability of metabotropic glutamate receptor activation to mobilise intracellular calcium was investigated in cultured dorsal root ganglion (DRG) neurones from neonatal rats using the calcium sensitive fluorescent dye Fura-2. L-glutamate (10 microM) caused sustained and oscillatory increases in intracellular calcium concentration ([Ca2+]i) in a subpopulation of cultured DRG neurones. The oscillatory responses were not blocked by combined application of the ionotropic glutamate receptor antagonists MK 801 (2 microM) and CNQX (20 microM). Oscillations in [Ca2+]i were also observed following application of the nonselective metabotropic glutamate receptor (mGluR) agonist, trans-(1S,3R)-1-aminocyclopentane-1S, 3R-dicarboxylic acid (1S,3R)-ACPD, 20 microM) and the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG, 500 microM). These responses were blocked by the selective Group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) (100 microM) and Ca2+ release channel inhibitors ryanodine (100 microM) and dantrolene (10 microM). The predominantly Group II agonist (2S,2'R,3'R)-2-(2'3'-dicarboxy-cyclopropyl)glycine (DCG-IV, 100 microM) failed to produce Ca2+ transients alone but suppressed responses to CHPG. Reverse transcriptase PCR techniques, using primers specific to Group I mGluRs, revealed the presence of mGluR5 but not mGluR1 mRNA in these cells. Therefore, glutamate can cause a slowly activating and reversible mobilisation of [Ca2+]i in sensory neurones by activation of ionotropic receptors, and can induce oscillatory calcium transients by selectively activating metabotropic glutamate receptors that are likely to be of the mGluR5 subtype.
Animals↗
Regional and cellular localization of calcitonin gene-related peptide-receptor component protein mRNA in the guinea-pig central nervous system.
Recent cloning studies have isolated proteins which confer responsiveness to calcitonin gene-related peptide (CGRP). In this study, we have determined the central nervous system (CNS) distribution of the mRNA of one such protein, termed CGRP-receptor component protein (RCP), by in situ hybridization. CGRP-RCP mRNA was widely expressed in the guinea-pig CNS, being particularly abundant in cerebellum and hippocampus. These data should assist in the determination of the potential physiological function(s) of this protein in the CNS.
Animals↗
Distribution of novel CGRP1 receptor and adrenomedullin receptor mRNAs in the rat central nervous system.
Recent cloning studies have isolated receptors which confer specific responsiveness to calcitonin gene related peptide (CGRP) and the related peptide adrenomedullin. Using in situ hybridisation, we demonstrate the heterogenous distribution of the mRNAs of two proposed CGRP1 receptors (RDC-1 and calcitonin receptor-like receptor, CRLR) in the rat brain. Adrenomedullin receptor mRNA was weakly expressed, principally in the cerebellum. These findings may assist in the determination of the function of these largely uncharacterised receptors.
Amygdala↗
Retrieval of cellular mRNA in paraffin-embedded human brain using hydrated autoclaving.
The aims of this study were to determine the optimal pretreatment of paraffin-embedded human brain sections for in situ hybridization using oligonucleotide probes. A selection of heating and enzymatic methods were compared and their effect on tissue morphology in addition to their ability to sensitise hybridization signal was investigated. In situ hybridization was carried out using a [35S]dATP 3'-end-labeled 30 base oligonucleotide specific for the human N-methyl-D-aspartate (NMDA) NR1-1 receptor subunit. In human hippocampus, NMDA NR1-1 mRNA was detected in the dentate gyrus, CA1, CA2 and CA3 pyramidal neurons and subiculum. The optimal pretreatment of paraffin-embedded sections was autoclaving in citrate buffer, pH 6.0. This novel technique was as sensitive as carrying out in situ hybridization on routinely used fresh-frozen, post-fixed sections, but offers significant advantages including preservation of superior morphology, more efficient, safe and stable storage dynamics and ability to conduct in situ hybridization and immunohistochemical detection methods on adjacent or identical sections.
Aged↗
Automated information systems for OR management.
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Hospital Information Systems↗
Individual variation in the isotype profile of anti-histone autoantibodies in systemic lupus erythematosus.
Using a solid-phase radioimmunoassay we have measured levels of anti-histone autoantibodies of the IgG, IgA and IgM heavy chain classes in 40 patients with systemic lupus erythematosus. Twenty-two patients (55%) had significantly elevated levels of at least one anti-histone isotype. Our results reveal four characteristics of the anti-histone response. (1) There is wide variation between patients in the isotype profile of anti-histone antibodies and these isotype profiles are a consistent individual characteristic. (2) There is no significant correlation between the level of IgG, IgA and IgM anti-histone in individual patients and a marked tendency for a single isotype (either IgG, IgA or IgM) to predominate in any one patient. (3) IgG anti-histone antibodies are predominantly of the IgG1 subclass. (4) Among 12 patients tested, IgG and IgA antibodies showed a preference for histones 1 and 2B whereas IgM antibodies showed no consistent preference for individual histones.
Adult↗
Platelets in the synovial fluid of patients with rheumatoid arthritis.
In a study of synovial fluid from 110 patients with various forms of arthritis, platelets were identified in the synovial fluid of all the 50 rheumatoids, in 18 out of the 25 (72%) with osteoarthritis and in all 35 of those with other forms of inflammatory osteoarthrosis. Identification of platelets by light microscopy was confirmed by electron microscopy. Platelet counts were significantly higher in rheumatoid fluid (mean 14 988/mm3; range 1000-65 000/mm3) compared with fluid from patients with osteoarthrosis (mean 1 592/Mm3; 0-10 000/mm3). In addition, significantly higher platelet counts were found in the synovial fluid (SF) of inflamed joints. There was a positive correlation between the SF platelet count and the total white cell count, polymorph count, hydrogen ion concentration, knee score, acid phosphatase and 5-nucleotidase activity and a negative correlation with the glucose level. All these factors indicate joint activity. Finally, platelet numbers correlated with SF levels of immunoglobulin M, and seropositive patients had significantly higher platelet counts in the SF compared with seronegative patients. Rheumatoid patients with thrombocytosis also had higher SF platelet counts. The close relationship of the SF platelet count to other indices of inflammation supports the concept that platelets may directly contribute to synovial inflammation by a variety of pathways.
Arthritis↗
Sterilization of laparoscopes. Is soaking sufficient?
Controversy exists over the proper methods of sterilizing laparoscopic telescopes. An edict requiring gas sterilization rather than solution soaking of these instruments is in force in all federal hospitals. This rule has necessitated capital investments for new instruments and has led to a severe reduction in the number of cases of laparoscopy that may be scheduled in one day. Fear of contamination is based on theoretical considerations and rusn counter to the actual, observed safety record seen with laparoscopes soaked in activated glutaraldehyde between cases. In an effort to dispassionately approach this problem, cultures of the umbilical area, the laparoscope and the pelvic serosal surfaces were taken to document the type of organisms commonly encountered under clinical conditions. Cultures for aerobic and anaerobic bacteria as well as for fungi were taken after soaking the telescope in activated glutaraldehyde. The results demonstrated growth of common skin organisms even after skin preparation with povidone-iodine and ethyl alcohol. Similar organisms were recovered in some cases from the laparoscope and the pelvic surfaces. The actual degree of contamination suggested by a colony count falls well within the range of the healthy peritoneum to cope with these organisms. Recommendations for laparoscopic sterilization or disinfection are based on the results obtained.
Ascitic Fluid↗
Prevention--everybody's responsibility.
The importance of individual responsibility in many aspects of preventive medicine is emphasised in the introduction. A section on infectious disease as applied to Western society today follows with special mention of particular conditions such as turberculosis, influenza, rubella, gastro-intestinal diseases and Legionaire's Disease. The section on non-communicable disease is subdivided into coronary heart disease, malignant neoplasms and chronic bronchitis. It includes some discussion of screening. Short sections on prevention in the elderly, pregnancy and early life, dental health, accidents, alcoholism and drug misuse follow. In the conclusions the difficulty of determining priorities for different societies and the importance of establishing cost effectiveness of preventive measures are covered. The relative importance of societal, governmental and individual preventive measures are described and the authors emphasise that any expensive screening programme must adhere to established criteria.
Accident Prevention↗