Gap between death rates of rich and poor widens.
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England↗
Biomedical subjects
R Smith
Publications and source records attributed to R Smith.
Lateralized changes in regional cerebral blood flow during performance of verbal and facial recognition tasks: correlations with performance and "effort".
Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional 133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET 15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks-using both absolute and relative (region/ whole brain) CBF. Replicating the 133Xenon clearance findings, CBF was "appropriately" lateralized during task performance (left-right for words > left-right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with "mental effort" indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.
Adult↗
Clinical and economic outcomes of expanded criteria donors in renal transplantation.
Although graft and patient survival rates were similar between recipients of kidneys from ECDs and non-ECDs, transplantation with organs from ECDs was significantly more expensive. Multivariate analysis using stepwise linear regression demonstrated length of stay to be a strong proxy for total hospital costs. Inherent tensions between the overall good clinical outcomes associated with the use of ECDs in terms of graft survival and the markedly increased costs seen with these organs are evident.
Age Factors↗
Long-term outcome of kidney transplantation from expanded criteria donors: a single center experience.
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Actuarial Analysis↗
Systemic lupus erythematosus-associated lymphoproliferative disorder: report of a case and discussion in light of the literature.
A case of autoimmune disease-associated lymphadenopathy (ADAL) with histological, immunophenotypic, Epstein-Barr virus (EBV) in situ hybridization, and genotypic analyses is presented. The patient had a well-documented history of systemic lupus erythematosus (SLE) and was found at autopsy to have massive lymphadenopathy, thymic enlargement, pulmonary nodules, and polyclonal serum dysproteinemia. Histological examination revealed a polymorphous lymphoid infiltrate containing many plasma cells, rare immunoblasts, and a pronounced arborizing vasculature. No foci of necrosis were found and there was no evidence of lymphocyte depletion. The plasma cells were immunophenotypically polyclonal and no EBV mRNA (EBER-1) or gene rearrangements were identified. The unusual gross features, which resembled a malignant lymphoproliferative process, as well as the unusual histological features make this case a notable addition to the spectrum of atypical lymphoproliferative disorders associated with an autoimmune disorder. We conclude that although reminiscent of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD), this case lacks the diagnostic features of AILD, and is, perhaps, best classified as an autoimmune disease-associated lymphadenopathy (ADAL).
Adult↗
Innervation of the mandibular incisors by the mental nerve.
PURPOSE: This study tested the hypothesis that some sensory innervation to the lower incisor teeth comes from reentry of the terminal branches of the mental nerve through the labial plate of the anterior mandible. PATIENTS AND METHODS: Ten cadaveric heads (20 sides) were dissected and studied to determine whether the mental nerve crossed the midline or reentered the labial plate. Using careful dissection, the most posterior branch of the nerve was exposed from its point of emergence at the mental foramen to its insertions, and any entries into the labial plate were recorded and photographed. RESULTS: Three of 20 (15%) specimens showed unequivocal evidence of nerve reentry into the labial plate. Five specimens displayed strong evidence of nerve fibers reentering the plate, but these were too fragile to be dissected through the periosteum without breaking. In 12 of 20 (60%) specimens, there were no branches identified that reentered the bone plate. Of the eight specimens showing evidence of reentry, four had substantial midline crossover. CONCLUSIONS: The finding that branches of the mental nerve may reenter the labial plate to supply the lower incisors explains the phenomenon of crossover innervation from the contralateral mental nerve and the fact that a labial infiltration injection will anesthetize the lower incisor teeth.
Anesthesia, Dental↗
Temporal bone analysis of patients with presbycusis reveals high frequency of mitochondrial mutations.
Presbycusis is a histologically and genetically heterogenous group of disorders, which lead to progressive, primarily sensorineural hearing loss with aging. Acquired mitochondrial DNA defects have been proposed as important determinants of aging, particularly in neuro-muscular tissues. The spiral ganglion and membranous labyrinth from archival temporal bones of 5 patients with presbycusis were examined for mutations within the mitochondrially-encoded cytochrome oxidase II gene. When compared to controls, results indicate that mitochondrial mutations in the peripheral auditory system occur commonly with age-related hearing loss, that there is great individual variability in both quantity and location of mutation accumulation, and that at least a proportion of presbycusis patients have a highly significant load of mutations in auditory tissue. This work supports the hypothesis that acquired mitochondrial mutations are a determinant of hearing loss in a subgroup of presbycusis patients.
Aged↗
49th ENMC-Sponsored International Workshop: fibrodysplasia (myositis) ossificans progressiva (FOP). 14-16 February 1997, Naarden, The Netherlands.
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Humans↗
Protection of sensitive patient-connected medical devices from the subversive use of mobile telecommunication equipment.
The UK Department of Health has recently advised caution with respect to the uncontrolled use of private mobile telecommunication equipment in designated sensitive hospital areas. This advice, which has clear implications for patient safety and well being, was issued following reports of the interference of automatic drug delivery devices, infusion pumps and other sensitive systems. The difficulty of monitoring relatives, visitors and, occasionally, staff who use such mobile telephones in the sensitive areas has led to an initiative by The Princess Margaret Hospital to automatically and continuously monitor the frequencies used by the mobile telephones and to initiate an alarm should such phones be used within a designated area. This paper describes a protocol for the use of these monitors developed in the Princess Margaret Hospital which is designed to minimize the number of monitoring units while providing optimum departmental cover.
Artifacts↗
Comparison of full thickness skin graft "take" after excision with the carbon dioxide laser and scalpel.
SPECIFIC AIM. To evaluate the take of skin grafts on conventionally prepared beds and on beds prepared by a carbon dioxide laser, with and without abrasion of the bed. SIGNIFICANCE. Graft take is dependent on hemostasis, immobility, and nutrition of the graft. Scalpel excision of the skin graft can be associated with hemostatic difficulties and laser treatment of the skin graft bed can provide hemostasis. Abrasion of the bed after laser treatment may then be a means of opening small lymphatic and blood vessels to maintain the graft. Laser treatment followed by abrasion of the bed may provide an ideal graft base before suturing of the skin graft. MATERIAL AND METHODS. Full-thickness skin grafts were taken with a scalpel at three sites on the dorsal skin of 24 guinea pigs. The three beds were prepared with pressure alone to provide hemostasis, laser vaporization followed by abrasion with gauze to produce pinpoint bleeding, and laser vaporization alone. The original skin from each of the sites was then sutured back in place. At postoperative days 1, 3, 5, 10, 21, and 35 the graft sites were assessed clinically for "take." Laser Doppler measurements were also made to evaluate blood flow. Histologic sections of the three sites were prepared. Immunohistochemical analysis was performed to evaluate cell proliferation and angiogenesis. RESULTS. For the animals sacrificed through day 10 the rate of take for the sites that were not lased was 100%. For the sites that were lased alone and lased and abraded the rate of take was 71% with no difference between the two techniques. The lased sites demonstrated increased inflammatory response and graft necrosis. Immunohistochemical analysis showed increased cellular proliferation and angiogenesis in the bed. DISCUSSION. Grafts take best on a scalpel-prepared bed. Laser preparation of the bed, with or without abrasion, demonstrates decreased "take." Therefore the carbon dioxide laser is not a recommended means to take a graft or prepare the graft bed.
Animals↗
Drug-motif-based diverse monomer selection: method and application in combinatorial chemistry.
This article describes a strategy to explore monomer diversity while incorporating drug motif knowledge into the design and selection of monomers for combinatorial chemistry. The process involves collecting from available electronic databases all those molecules that potentially could be monomers. In this manner we have assembled five DAYLIGHT databases, each containing one of the common functional groups: carboxylic acids, aldehydes, nitriles, primary amines, and secondary amines. The molecules in the databases are then subjected to fingerprint and cluster analysis using the Jarvis-Patrick algorithm and profiles of the compounds are calculated relating to molecular weight, H-bond counts, and rotatable bond flexibility. The cluster information and profiles of the molecules are stored back into the databases for similarity and diversity searches, and for profile prescreening of monomers. To apply drug motif knowledge to a selection an application to an aldehyde set is discussed, in which representatives of each cluster in the aldehyde database are compared with drug molecules in the Standard Derwent File (SDF) in one of three ways to select drug motif-based monomers for purchase or synthesis.
Aldehydes↗
Inhibitory effects of CAI in glioblastoma growth and invasion.
While distant metastases are rare in patients with primary brain malignancies, local growth and invasion are common and life-threatening. Regional infiltration is responsible for the failure of local therapies, resulting in tumor recurrence, progression, and death. The process of invasion requires cellular adhesion, local proteolysis and migration. CAI, carboxyamide-triazole, is an anticancer agent developed as an inhibitor of selected signal transduction pathways. Studies on the effects of CAI on human glioblastoma growth and invasiveness are presented. CAI inhibited proliferation of 6 of 8 cell lines tested in a dose-dependent fashion in vitro (IC50 range 1.5-44 microM), with no effect on the U373 line. Inhibition of adhesion to tissue culture plastic was observed for the H4, T98G, and U373 lines pretreated with CAI; H4 and T98G were inhibited in adhesion to collagen type IV. Incubation with CAI decreased production of the 72 kDa and 92 kDa type IV collagenases in all cell lines, ranging from 16 to 93% inhibition. These observations show that the effects of CAI on cell line behavior can vary between lines that are similar in origin. Despite variability in the inhibitory effects for proliferation and adhesion, CAI is consistently able to inhibit the invasive phenotype of all glioma cell lines in vitro using the Matrigel barrier assay (IC50 range 13-28 microM). These observations suggest that CAI may have benefit in the treatment of gliomas and high grade astrocytomas.
Antineoplastic Agents↗
The structure of a novel insecticidal neurotoxin, omega-atracotoxin-HV1, from the venom of an Australian funnel web spider.
A family of potent insecticidal toxins has recently been isolated from the venom of Australian funnel web spiders. Among these is the 37-residue peptide omega-atracotoxin-HV1 (omega-ACTX-HV1) from Hadronyche versuta. We have chemically synthesized and folded omega-ACTX-HV1, shown that it is neurotoxic, ascertained its disulphide bonding pattern, and determined its three-dimensional solution structure using NMR spectroscopy. The structure consists of a solvent-accessible beta-hairpin protruding from a disulphide-bonded globular core comprising four beta-turns. The three intramolecular disulphide bonds from a cystine knot motif similar to that seen in several other neurotoxic peptides. Despite limited sequence identity, omega-ACTX-HV1 displays significant structural homology with the omega-agatoxins and omega-conotoxins, both of which are vertebrate calcium channel antagonists; however, in contrast with these toxins, we show that omega-ACTX-HV1 inhibits insect, but not mammalian, voltage-gated calcium channel currents.
Amino Acid Sequence↗
Application of tryptamine as a derivatizing agent for the determination of airborne isocyanates. Part 7. Selection of impinger solvents and the evaluation against dimethyl sulfoxide used in US NIOSH Regulatory Method 5522.
The application of tryptamine to derivatize airborne isocyanates has been evaluated and adopted by the National Institute for Occupational Safety and Health (NIOSH) as the latest isocyanates regulatory method (Method 5522) in the USA. Method 5522 uses dimethyl sulfoxide (DMSO) as the impinger solvent in which tryptamine is dissolved to sample isocyanates for analysis. Since DMSO is both extremely hygroscopic and corrosive, it is not a satisfactory solvent for impinger air sampling of isocyanates. The high boiling and freezing points also present some distinct drawbacks. In a search for a suitable impinger solvent, the efficiencies of various solvents, which all were potentially more suitable for sampling isocyanates viz., N,N'-dimethylformamide, butyl acetate, isobutyl acetate, sec-butyl acetate, tert-butyl acetate and octane, were investigated. Simulated air sampling was conducted on two commonly used isocyanates in industry, hexamethylene diisocyanate (HDI) and toluene diisocyanate (TDI), which were vaporized and sampled into impingers containing dissolved tryptamine. Butyl acetate and octane were found to be most suitable for using as impinger solvents. Recoveries of isocyanates at two concentration levels of HDI and TDI were 93.4-108% in comparison with those of using DMSO.
Air Pollutants, Occupational↗
Incomplete holism in pre-registration nurse education: the position of the biological sciences.
There is an ongoing debate in nurse education concerning the role and delivery of the biological sciences in the nursing curriculum. One of the fundamental questions raised by this debate asks how best can teachers impart biological knowledge in a manner that can be readily applied by students and qualified nurses to inform their clinical practice. This paper will include a discussion of some of the features of pre-registration education that may have influenced the manner in which biological sciences are perceived, taught and used by nurses. It will be argued that nursing may have developed a form of incomplete holism and that this may be in part responsible for the challenges that remain to be met within this area of the nursing curriculum. As a response to incomplete holism an innovative approach within pre-registration education will be introduced. This development involves the use of linked teaching sessions which aim to develop the analytical skills necessary to apply physiological knowledge to nursing practice.
Biological Science Disciplines↗
Atrial natriuretic peptide, cyclic GMP analogues and modulation of guanylyl cyclase do not alter stimulated POMC peptide release from perifused rat or sheep corticotrophs.
Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are two potent stimulators for secretion of proopiomelanocortin (POMC)-derived hormones, from corticotrophs. CRH also stimulates POMC synthesis. Atrial natriuretic peptide (ANP) has been reported to inhibit POMC peptide release and is thought to act through cGMP signalling pathways. A multicolumn cell perifusion system was used to investigate the role of cGMP signalling pathways in CRH- and AVP-stimulated POMC peptide release from primary cultures of ovine or rat anterior pituitary cells. The CRH and/or AVP stimulations were applied at 30 min intervals as 5 min pulses, and the various treatments were infused over a period of 50 min, overlapping with 2 of the stimulations. ANP (10 nM) had no effect on beta-endorphin (betaEP) release from ovine cells, stimulated by 0.5 nM CRH and 5 nM AVP together, or 5 nM CRH and 50 nM AVP separately. Rat anterior pituitary cells were stimulated with 0.05 nM CRH/0.5 nM AVP or 0.5 nM CRH/5 nM AVP and treated with 1 nM or 10 nM ANP, respectively. No inhibition of ACTH or betaEP was observed. Similarly, the nitric oxide donors molsidomine (100 microM), SIN-1 (100 microM) and NaNO2 (100 microM) did not inhibit betaEP release stimulated by 0.5 nM CRH/5 nM AVP in ovine cells. The cGMP analogues 8-bromo-cGMP (10 microM and 100 microM) and dibutyryl cGMP (100 microM) also had no effect on betaEP and ACTH release from ovine or rat anterior pituitary cells. Dexamethasone (8 microM), a synthetic glucocorticoid known to block POMC synthesis and secretion of betaEP and ACTH by a distinct mechanism, was used as a control and suppressed CRH/AVP-stimulated betaEP secretion from ovine anterior pituitary cells. These results contrast with some previous studies and demonstrate that the cGMP signalling pathway in sheep or rat anterior pituitary cells does not directly inhibit secretion of POMC-derived hormones from corticotrophs.
Animals↗
Relationships among msx gene structure and function in zebrafish and other vertebrates.
The zebrafish genome contains at least five msx homeobox genes, msxA, msxB, msxC, msxD, and the newly isolated msxE. Although these genes share structural features common to all Msx genes, phylogenetic analyses of protein sequences indicate that the msx genes from zebrafish are not orthologous to the Msx1 and Msx2 genes of mammals, birds, and amphibians. The zebrafish msxB and msxC are more closely related to each other and to the mouse Msx3. Similarly, although the combinatorial expression of the zebrafish msx genes in the embryonic dorsal neuroectoderm, visceral arches, fins, and sensory organs suggests functional similarities with the Msx genes of other vertebrates, differences in the expression patterns preclude precise assignment of orthological relationships. Distinct duplication events may have given rise to the msx genes of modern fish and other vertebrate lineages whereas many aspects of msx gene functions during embryonic development have been preserved.
Amino Acid Sequence↗
A comparison of hemodynamic parameters derived from transthoracic electrical bioimpedance with those parameters obtained by thermodilution and ventricular angiography.
OBJECTIVE: To determine the limits of agreement between the cardiac output and volumetric data estimated by impedance cardiography with the cardiac output determined by thermodilution and the left ventricular ejection fraction and end-diastolic volume estimated from left ventriculography. DESIGN: A prospective study. SETTING: The cardiac catheterization laboratory of a university-affiliated teaching hospital. PATIENTS: Twenty-four patients with coronary artery disease undergoing elective left- and right heart catheterization. INTERVENTIONS: Cardiac output was measured by the thermodilution method and the ejection fraction and left ventricular volumetric data were determined by ventriculography. These same measurements were obtained by simultaneously performed impedance cardiography using a commercially available bioimpedance device. MEASUREMENTS AND MAIN RESULTS: The patients' mean cardiac output was 4.6 +/- 1.7 L/min by bioimpedance and 5.0 +/- 1.1 L/min by thermodilution. The limits of agreement between the two methods was -4.1 to 3.5 L/min. The 95% confidence intervals for the lower and upper limits of agreement were -2.7 to -5.5 L/min and 2.1 to 4.9 L/min, respectively. The mean ejection fraction was 63 +/- 8% by bioimpedance and 53 +/- 15% by ventriculography. The limits of agreement between the ejection fraction estimated by bioimpedance and ventriculography was -35% to 37%. The 95% confidence intervals for the lower and upper limits of agreement were -22% to -48% and 24% to 50%, respectively. The mean left ventricular end-diastolic volume was 108 +/- 47 mL, as estimated by bioimpedance, and 121 +/- 35 mL, as estimated by ventriculography. The limits of agreement between the left ventricular end-diastolic volume as estimated by bioimpedance and ventriculography was -139 to 113 mL. The 95% confidence intervals for the lower and upper limits of agreement were -184 to -94 mL and 68 to 158 mL, respectively. CONCLUSIONS: The 95% confidence range defining the limits of agreement between cardiac output and volumetric data estimated by bioimpedance, with the cardiac output measurement by thermodilution and the volumetric data estimated from left ventriculography, were wide, making the degree of agreement clinically unacceptable. In the opinion of the authors, impedance cardiography should not replace invasive hemodynamic monitoring at this time.
Aged↗