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Biomedical subjects

L Shaw

Publications and source records attributed to L Shaw.

At least 73 records · Page 4Linked to original sources

The presence of N-acetylneuraminic acid in Malpighian tubules of larvae of the cicada Philaenus spumarius.

Sialic acid-containing glycoconjugates are generally considered to be unique to the deuterostomes, a lineage of the animal kingdom which includes animals from the echinoderms up to the vertebrates. There are, however, two isolated reports of sialic acid occurring in the insect species Drosophila melanogaster and Galleria mellonella. Since insects are classified as protostomes, these findings call previous assumption on the phylogenetic distribution and thus on the evolution of sialic acids into question. Here, we report the occurrence of N-acetylneuraminic acid (Neu5Ac) in larvae of the cicada Philaenus spumarius. Cytochemical analysis of larval sections with lectins from Sambucus nigra and Limax flavus suggested the presence of sialic acids in the concrement vacuoles of the Malpighian tubules. The monoclonal antibody MAb 735, which is specific for polysialic acid, labelled the same structures. A chemical analysis performed by HPLC of fluorescent derivatives of sialic acids and by GLC-MS provided sound evidence for the presence of Neu5Ac in the Philaenus spumarius larvae. These data suggest that in this cicada Neu5Ac occurs in alpha2,8-linked polysialic acid structures and in alpha2,6-linkages. The results provide further evidence for the existence of sialic acids in insects and in linkages known to occur in glycoconjugates of deuterostomate origin.

Animals↗

A comparison of sampling and analytical methods for assessing occupational exposure to diesel exhaust in a railroad work environment.

Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work environment. The American Conference of Governmental Industrial Hygienists (ACGIH)-recommended elemental carbon and respirable combustible dust methods of sampling and analysis for assessing diesel exhaust were included in the study. A total of 215 personal and area samples were collected using both size-selective (nylon cyclone and Marple) and non-size-selective samplers. The results demonstrate that the elemental carbon method is suitable for the railroad environment and the respirable combustible dust method is not. All elemental carbon concentrations measured were below the proposed ACGIH Threshold Limit Value (TLV) of 0.15 mg/m3. The concentrations of oxides of nitrogen (nitric oxide and nitrogen dioxide) were also found to be below their respective TLVs. There is no correlation between elemental carbon or respirable combustible dust and the oxides of nitrogen. The elemental carbon as fraction of total carbon is about 13 percent, except for onboard locomotives where it is about 24 percent. Comparison of elemental carbon and respirable combustible dust measurements showed consistent relationships for most sampling locations, with respirable combustible dust concentrations 12 to 53 times higher than the elemental carbon levels.

Data Interpretation, Statistical↗

Laboratory confirmation of scopolamine co-intoxication in patients using tainted heroin.

BACKGROUND: First described in 1995, at least 325 patients with a history of heroin use have since required emergency medical evaluation in several eastern US cities, because of an anticholinergic toxidrome following use of heroin. This co-intoxication has been alleged to result from an atropine-like compound. We report the clinical findings and laboratory analysis of one of several individuals who presented to our Emergency Department during this epidemic. CASE REPORT: A 23-year-old male was one of 3 patients brought to the Emergency Department due to agitated behavior after insufflating heroin. Following physical and chemical restraint, vital signs were pulse 134 bpm, BP 160/90 mm Hg, RR 24/min, and T 37.3 degrees C. Physical examination was remarkable for dilated pupils 8-9 mm without nystagmus, along with dry mouth, decreased bowel sounds, and flushed dry skin. A bladder catheter was placed and 500 mL of urine was obtained. Electrocardiogram revealed sinus tachycardia only. Additional sedation was required for 12 hours until normal mental status returned. A small sample of the "heroin" used was obtained and analyzed. Scopolamine was confirmed by gas chromatography-mass spectrometry. Further evidence of scopolamine intoxication was supported by identifying scopolamine in the urine of this patient. CONCLUSION: Gas chromatography-mass spectrometry revealed scopolamine to be the cause of anticholinergic findings in a patient following use of tainted heroin. It is unclear whether scopolamine is an adulterant or contaminant in this heroin. Patients with anticholinergic findings following use of heroin may be co-intoxicated with scopolamine.

Adult↗

Predictive properties of a qualitative urine acetaminophen screen in patients with self-poisoning.

OBJECTIVE: Screening for acetaminophen toxicity is recommended in almost all cases of self poisoning. We compared a qualitative urine acetaminophen screen to the quantitative serum acetaminophen to test the hypothesis that a negative urine acetaminophen screen would be predictive of a negative serum acetaminophen level. METHODS: All adults with intentional ingestions evaluated in our Emergency Department during 1995 were retrospectively identified based on Emergency Department International Classification of Disease--9th edition codes. Laboratory data from each patient including serum and urine toxicologic assays were examined. Predictive properties of urine acetaminophen screens for serum acetaminophen were evaluated. RESULTS: A total of 88 patients were identified who had both a serum acetaminophen and a urine acetaminophen performed. The sensitivity of the urine acetaminophen screen was 100% (95% CI 72-100%) and the specificity was 87% (95% CI 80-95%). All patients with negative urine acetaminophen screens had negative serum acetaminophen levels (negative predictive value 100%; 95% CI 96-100%). Accuracy of the urine acetaminophen screen was 89%. CONCLUSION: A negative urine acetaminophen screen was highly predictive of negative serum acetaminophen levels. It is possible that negative urine acetaminophen screens may obviate the need for 4-hour quantitative serum levels. Further validation in a prospective study is needed.

Acetaminophen↗

Repetitive strain injuries in dentistry.

In order to avoid RSI, try to neutralize, modify and energize at work, home and play. These concepts eliminate the risk factors associated with the development of RSI and optimize an individual's physical capabilities to work productively and efficiently. People suffering with an RSI should consult their physician regarding the various treatment options available to them. Ideally, prevention is the key to reducing the costs and problems associated with RSI. However, an individual suffering with RSI should not delay addressing the injury. Treatment is most effective when applied as soon as possible after the onset of injury.

Cumulative Trauma Disorders↗

The biosynthesis of 8-O-methylated sialic acids in the starfish Asterias rubens--isolation and characterisation of S-adenosyl-L-methionine:sialate-8-O-methyltransferase.

The unusual, 8-O-methylated sialic acids have only been found in glycoconjugates of certain species of starfish. Using a detergent-solubilised extract of a particulate fraction from gonads of Asterias rubens, a specific methylation of endogenous and exogenous glycoconjugate-bound sialic acids was detected with [14C]-S-adenosyl-L-methionine ([14C]AdoMet) as the methyl donor. For this test, a filtration assay was developed using glutardialdehyde-fixed horse erythrocyte membranes as methyl acceptor. The enzyme catalysing this reaction, the sialate-8-O-methyltransferase, was purified 22000-fold in a yield of 13% by ion-exchange chromatography and two cycles of affinity chromatography on S-adenosyl-L-homocysteine-Sepharose. Upon SDS/PAGE under reducing conditions, the purified sialate-8-O-methyltransferase revealed two bands with apparent molecular masses of 58 kDa and 62 kDa. Since no evidence for the presence of subunits was found, the relationship between these two species is unknown. The enzyme was optimally active over a broad range of pH (7.4-8.3) and at 37 degrees C. After EDTA treatment, restoration of the activity depended, in contrast to most methyltransferases, on Mn2+ or Co2+, the latter to a lesser extent. Although both, free N-acetylneuraminic acid and N-glycoloylneuraminic acid were methylated, sialic acids alpha-glycosidically bound to a number of oligosaccharides and glycoproteins were better substrates. In the presence of 20 microM AdoMet, apparent Km values of 299 microM and 44 microM were found for N-acetylneuraminic acid and N-acetylneuraminyl alpha2,3-lactose, respectively. Using N-acetylneuraminyl alpha2,3-lactose as acceptor, an apparent Km of 7.1 microM was found for S-adenosyl-L-methionine. Therefore, the sialate-8-O-methyltransferase is the first enzyme known to modify both free and glycoconjugate-bound sialic acids.

Animals↗

Antigen-independent suppression of the IgE immune response to bee venom phospholipase A2 by maternally derived monoclonal IgG antibodies.

The IgE immune response to ovalbumin in rats can be suppressed by prior immunization of the dams. The results reported in this paper extend this observation to include a different antigen and another species, namely the IgE immune response to bee venom phospholipase A2 (PLA2) in CBA/J mice. The degree of suppression seemed to depend on the amount of IgG antibodies transferred to the offspring. Moreover, we found that the maternally mediated suppression of the IgE response could be achieved in a completely antigen-free system in which exogenous monoclonal anti-PLA2 IgG antibodies were transferred from the dams to the offspring. The following results were obtained: (i) The IgE suppression by monoclonal IgG antibodies was induced as efficiently with one single anti-PLA2 IgG1 antibody as with a mixture of ten antibodies (nine IgG1, one IgG2b). (ii) Even after several immunizations up to an age of 6 months with a dose of PLA2 that normally induces IgE production, none of the F1 mice developed an IgE response. (iii) This long-lasting suppression was observed in mice which were first immunized at an age of 4 weeks (i.e. when low amounts of maternally derived monoclonal IgG were still present), as well as in mice which were first immunized at an age of 8 weeks, when no such maternal antibodies could be detected in their sera. The corresponding IgG responses showed, compared to normal mice, a transient enhancement in the maternally influenced mice. It is concluded that the immunological experience of the mother is of particular importance for the isotype regulation in the newborns, especially with respect to the ability to elicit an IgE response. The possible implications for the development of allergic diseases in humans are discussed.

Animals↗

Cytidine monophosphate-N-acetylneuraminate hydroxylase in the starfish Asterias rubens and other echinoderms.

The sialic acid N-glycolylneuraminic acid (Neu5Gc) is synthesised by an NADH-dependent hydroxylase which acts on CMP-N-acetylneuraminic acid (CMP-Neu5Ac). Although Neu5Gc is the predominant sialic acid in many echinoderms, little is known about the hydroxylase from organisms of this phylum. We show here that in contrast to the mammalian enzyme, the hydroxylase from various echinoderms is predominantly membrane-bound and exhibits optimal activity in the presence of 100 mM NaCl. A detailed characterisation of the hydroxylase from echinoderms was performed using fractionated gonads of the starfish Asterias rubens. Solubilisation using detergents led to an inactivation of the hydroxylase. However, the solubilised enzyme was reactivated by the addition of cytochrome b5 reductase together with the amphiphilic or soluble form of cytochrome b5. Although these latter proteins were only available from a mammalian source, the high affinity of the hydroxylase for cytochrome b5 suggests that, as with the mammalian enzyme, these electron carriers participate in the catalytic cycle of the hydroxylase from A. rubens in vivo. The relevance of these results to the interaction between cytochrome b5 and the hydroxylase is discussed.

Animals↗

Urinary calcium/creatinine ratio as a predictor of preeclampsia.

Hypocalciuria has been associated with preeclampsia (gestational hypertension with proteinuria or other maternal organ dysfunction) but not usually with pure gestational hypertension or normal pregnancy. We hypothesized that hypocalciuria would be a marker of emerging preeclampsia in women presenting with gestational hypertension who later developed preeclampsia. Eighty-one women with de novo hypertension in the second half of pregnancy (n = 81) were enrolled prospectively. At first assessment, calcium/creatinine ratio was determined in a spot urine. Patients were followed until delivery and were classified subsequently according to the occurrence of preeclampsia. Gestational hypertensive patients who became preeclamptic (n = 31) had lower urinary calcium/creatinine ratios at presentation (ratio = 0.07, interquartile range [IQR] = 0.04-0.11) than women who remained as gestational hypertensives (n = 50; ratio = 0.17, IQR = 0.08-0.21; P = .002). Intact plasma parathyroid hormone (PTH) concentrations were similar between groups. Using a receiver operator curve, the best threshold value for the development of preeclampsia was a calcium/creatinine ratio of 0.10, which yielded a sensitivity of only 68% and a specificity of 70%. A low calcium/creatinine ratio preceded the emergence of preeclampsia by 12 (7-24) (median [IQR]) days among a group of women with gestational hypertension. Though this implies primary or secondary disturbances of renal calcium handling even before preeclampsia is clinically apparent, this measurement does not have sufficient sensitivity to recommend its use as a screening test for the emergence of preeclampsia.

Adult↗

The role of CMP-N-acetylneuraminic acid hydroxylase in determining the level of N-glycolylneuraminic acid in porcine tissues.

The biosynthesis of the sialic acid N-glycolylneuraminic acid (Neu5Gc) occurs by the action of cytidine monophosphate-N-acetylneuraminate (CMP-Neu5Ac) hydroxylase. Previous investigations on a limited number of tissues suggest that the activity of this enzyme governs the extent of glycoconjugate sialylation with Neu5Gc. Using improved analytical procedures and a panel of nine porcine tissues, each expressing different amounts of Neu5Gc, we have readdressed the issue of the regulation of Neu5Gc incorporation into glycoconjugates. The following parameters were measured for each tissue: the molar ratio Neu5Gc/Neu5Ac, the activity of the hydroxylase, and the relative amount of hydroxylase protein, as determined by enzyme-linked immunosorbent assay (ELISA). A positive correlation between the activity of the hydroxylase and the molar ratio Neu5Gc/Neu5Ac was observed for each tissue. In addition, the hydroxylase activity correlated with the amount of enzyme protein, though in heart and lung disproportionately large amounts of immunoreactive protein were detected. Taken together, the results suggest that the incorporation of Neu5Gc into glycoconjugates is generally controlled by the amount of hydroxylase protein expressed in a tissue.

Animals↗

Human enamel as a substrate for in vitro acid dissolution studies: influence of tooth surface and morphology.

The variation in susceptibility of enamel to acid dissolution has been quantitatively assessed in vitro by examination of different surfaces of both maxillary and mandibular teeth of different morphology obtained from a pool of sound human teeth. The lingual/palatal surfaces of all teeth showed greater susceptibility to acid dissolution than the corresponding labial/buccal surfaces. The palatal surface of the maxillary teeth appeared more susceptible to acid than the lingual surface of the corresponding teeth in the mandible. The palatal surfaces of the maxillary teeth showed least variation in acid susceptibility, whilst the lingual surfaces of mandibular teeth and buccal/labial surfaces of teeth from both jaws showed much more variation between teeth of different morphology. These differences in susceptibility to acid dissolution probably reflect both developmental differences and post-eruptive changes in enamel and may contribute to the clinical presentation of dental disease. Importantly, the data indicates that careful selection of teeth for in vitro study of enamel dissolution processes is essential to minimise inter-sample variation. For such purposes, the palatal surface of the maxillary teeth appears to be most suitable.

Adult↗

Australian Incident Monitoring Study in intensive care: local unit review meetings and report management.

The Australian Incident Monitoring Study in the intensive care unit (AIMS-ICU) is a national study established through nursing and medical collaboration to develop, introduce and evaluate an anonymous voluntary incident reporting system. To ensure incident monitoring results in improved patient safety, it is essential that reported incidents are followed up regularly. Local unit review meetings are an effective forum for discussion and review of reports amongst a wide group of practitioners from the intensive care unit (ICU). All staff should be invited to participate in order to suggest preventative strategies, report on incident follow up and explore national study findings. Ongoing momentum of the project is assisted by highlighting its positive contributions to patient care and safety via newsletters, poster displays and targeted correspondence. New staff require orientation to the reporting system and assurance regarding safety of data. The emphasis must focus on the system, not the individual.

Australia↗

Problems associated with nursing staff shortage: an analysis of the first 3600 incident reports submitted to the Australian Incident Monitoring Study (AIMS-ICU).

Although many studies have attempted to define appropriate nursing staff levels, allocation and patient dependency, minimal data is available on the effect of nursing staff shortage (NSS) on quality of care provided in intensive care. This study aimed to identify incidents associated with staff shortage as reported to the Australian Incident Monitoring Study-ICU (AIMS-ICU) project and to assess their estimated effect on patient outcome. A search of narrative keywords and contributing factors identified 89 nursing staff shortage incidents (NSS-INCIDENTS) and 373 incidents involving nursing staff shortage contributing factors (NSS-CF). NSS resulted from inappropriate rostering for current patient load (81%) and inability to respond to increased unit activity (19%). Most frequent associated incidents included problems with: drug administration/documentation (47), patient supervision (20), set-up of ventilators/equipment (16), and accidental extubation (14). Undesirable patient outcomes included: major physiological change (22%), patient/relative dissatisfaction (12%), and physical injury (3%). This study suggests that inadequate staffing results in incidents and compromised patient safety.

Australia↗

Risk stratification in coronary artery disease: implications for stabilization and prevention.

Noninvasive nuclear imaging techniques, including dual-isotope myocardial perfusion single-photon emission computed tomography (SPECT), have been employed in the development of strategies for diagnosis and risk stratification of patients with suspected or known coronary artery disease. These risk-stratification strategies are based on studies in which known outcome has been linked to diagnostic and prognostic information provided by myocardial perfusion SPECT. This article describes a validated dual-isotope exercise protocol for assessment of perfusion and function and reviews the evidence on which a cost-effective risk management strategy is based.

Coronary Disease↗

Involvement of tyrosine phosphorylation in endothelin-1-induced calcium-sensitization in rat small mesenteric arteries.

1. We have studied the effect of endothelin-1 stimulation on protein tyrosine phosphorylation levels in intact small mesenteric arteries of the rat and investigated the effects of tyrosine kinase inhibition on the contractile response to this agonist. 2. Endothelin-1 stimulated a rapid (20 s), sustained (up to 20 min) and concentration-dependent (1-100 nM) increase in protein tyrosine phosphorylation levels which coincided temporally with the contractile response in intact and alpha-toxin permeabilized small artery preparations. Tyrosine phosphorylation was increased in four main clusters of proteins of apparent molecular mass 28-33, 56-61, 75-85 and 105-115 kDa. Endothelin-1-induced protein tyrosine phosphorylation was independent of extracellular calcium, antagonized by the tyrosine kinase inhibitor tyrphostin A23 but not by the inactive tyrphostin A1. 3. In intact small arteries tyrphostin A23 inhibited the force developed to endothelin-1 at all concentrations studied; at higher concentrations (10 and 100 nM) the profile of contraction was altered from a sustained to a transient response. Tyrphostin A1 inhibited the contractile response to endothelin-1 at all concentrations except 100 nM; the profile of the response was not altered. Neither tyrphostin affected the transient phasic contraction induced by endothelin-1 (100 nM) in the absence of extracellular calcium. 4. In rat alpha-toxin permeabilized mesenteric arteries endothelin-1 caused a concentration-dependent increase in force in the presence of 10 microM GTP and low (pCa 6.7) constant calcium, demonstrating increased sensitivity of the contractile apparatus to calcium. Tyrphostin A23 inhibited this response by approximately 50%, tyrphostin A1 did not affect endothelin-1-induced calcium sensitization of force. 5. We conclude that increased tyrosine phosphorylation is important in the contractile response induced by endothelin-1 in intact small mesenteric arteries. Furthermore our data implicate activation of this signalling pathway in the tonic phase of contraction possibly through modulation of the sensitivity of the contractile apparatus to calcium.

Animals↗

Protocol for detection and follow-up of hearing loss.

Hearing loss in one individual affects the lives of those who live and work with the person with the loss. Both the individual with the defined loss and the family must find adaptive methods of communicating. This article presents a protocol to be used by the advanced practice nurse in the assessment, intervention, and referral of patients suspected of having a hearing loss. It includes the family and social network as having an important role in this process. The year 2000 projected health objectives for the nation include health promotion goals to reduce significant hearing impairments. Research-based studies have identified the impact of hearing loss on the individual and the family. Intervention strategies and outcome measurements, therefore, must support a standardized protocol that focuses on hearing loss in the individual and promotes health in the family and social network.

Aftercare↗

Improved methods of assessing proteinuria in hypertensive pregnancy.

OBJECTIVE: To determine whether use of an automated urinalysis device will improve the accuracy of detecting proteinuria, and whether spot urine protein to creatinine ratio will provide accurate quantitation of proteinuria in hypertensive pregnant women. DESIGN: Prospective studies assessing the accuracy of both detection and quantitation of proteinuria. SETTING: Antenatal ward and pregnancy day assessment unit of St George Hospital, a teaching hospital in Sydney, Australia. POPULATION: Hypertensive pregnant women admitted to hospital or day assessment unit for management of their hypertensive disorders. METHODS: 1. Routine dipstick urinalysis and 2. urinalysis by an automated device (Clinitek 100 Ames) on a midstream urine sample were compared with measurement of protein concentration on that sample (n = 103). In a third study, the protein:creatinine ratio on a midstream (spot) urine sample was compared with protein excretion over the subsequent 24 hours (n = 100). MAIN OUTCOME MEASURES: Relations between urine protein concentrations and 1. dipstick urinalysis and 2. automated urinalysis; 3. Positive and negative predictive values of spot protein:creatinine ratio for true proteinuria (> or = 300 mg/day). RESULTS: Automated urinalysis improved the percentage of true positive urinalyses from 48% with visual urinalysis to 74% (P = 0.02). True negatives were 98% to 100% for both methods. Spot urine protein:creatinine ratio correlated well with subsequent 24-hour urine proteinuria (r = 0.93, P < 0.001). A protein:creatinine ratio > 30 mg protein/mmol creatinine was the optimum discriminant value for true proteinuria, with sensitivity 93%, specificity 92%, positive predictive value 95% and negative predictive value 90%. CONCLUSIONS: Use of an automated urinalysis device improved accurate detection of proteinuria, particularly reducing false positive tests. A random urine protein:creatinine ratio provides an accurate and rapid quantitation of proteinuria in hypertensive pregnant women. This should improve clinical care, especially when managing hypertensive pregnant women as outpatients.

Creatinine↗