Search PubMed⌕ Search

Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 343 records · Page 19Linked to original sources
PubMed1999

Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel.

We report an evaluation of current laboratory practice for the diagnosis of von Willebrand's disease (VWD) by means of a multilaboratory survey. This assessment was undertaken with the RCPA Quality Assurance Program (QAP) in Haematology, which covers a wide geographic area encompassing Australia, New Zealand and Asia. A total of 25 laboratories actively involved in testing for VWD were selected to participate in a sample testing assessment exercise. Samples comprised 10 plasmas: (i) a normal plasma pool (in duplicate), (ii) this pool diluted to 50% (in duplicate), (iii) a normal individual (X1), (iv) severe Type 1 VWD (X1), (v) Type 2B VWD (x2 unrelated donors), (vi) Type 3 VWD (x1), (vii) Type 2A VWD (x1). Laboratories were asked to perform all tests available to them in order to establish a laboratory diagnosis of VWD, and then to comment on the possibility or otherwise of VWD. Overall findings indicated a wide variation in test practice, in the effectiveness of various test procedures in detecting VWD, and in the ability of various composite test panels to identify type 2 VWD subtypes. Firstly, while all laboratories (n = 25) performed tests for FVIII:C activity, von Willebrand factor 'antigen' (VWF:Ag) and a functional VWF assay [using the ristocetin cofactor assay (VWF:RCo; n = 23) and/or the collagen binding assay (VWF:CBA; n = 12)], only three laboratories carried out VWF:Multimer analysis. Secondly, for the three quantitative VWF assays, 10/25 (40%) laboratories performed all three, whereas 15/25 (60%) performed only two [VWF:Ag and VWF:RCo (n = 13); VWF:Ag and VWF:CBA (n = 2)]. Thirdly, a variety of assay methodologies were evident for VWF:Ag [ELISA, electro-immuno diffusion (EID), latex immuno-assay (LIA), and VIDAS assay] and VWF:RCo (platelet agglutination/'aggregometry' and a 'functional VWF:RCo-alternative' ELISA assay). Between method analysis for the quantitative VWF assays showed that the VWF:RCo yielded the greatest degree of inter-laboratory assay variation, and had the poorest overall performance with respect to sensitivity to low levels of VWF. The VWF:CBA also performed better than the VWF:RCo in terms of ability to detect functional VWF 'discordance' (i.e. Type 2 VWD). Within VWF:Ag method analysis showed that the EID assay procedure was associated with the greatest variation in assay results, while the EID and LIA test methods showed poorer sensitivity at low VWF levels compared to the ELISA method. Within the VWF:RCo assay procedure, greatest variation in assay results and poorest sensitivity to low VWF levels was obtained using the agglutination method; however, the agglutination procedure showed better performance than the 'functional VWF:RCo-alternative' ELISA assay in identifying Type 2 VWD plasma samples. Finally, despite identified variations, most laboratories appeared to understand the complexities involved in the VWD-diagnostic process, and made appropriate diagnostic predictions regarding tested samples. From a total possible 246 interpretation events, laboratories in most cases correctly identified normal samples as normal (67/75 events = 89%), and VWD samples as derived from individuals with VWD (117/121 events = 97%). Moreover, when VWD was suggested by laboratory findings, laboratories usually correctly predicted the general subtype of VWD present (96/109 events = 88%). When 'misinterpretations' occurred, these could often be linked to the test panels utilised by laboratories. That is, laboratories using the VWF:Ag and VWF:RCo combination were more likely to incorrectly identify samples derived from Type 2 VWD patients as being Type 1, Type 1 VWD patients as being Type 2, and normal plasma samples as potentially derived from patients with VWD, compared to those using the VWF:Ag and VWF:CBA.

Clinical Laboratory Techniques↗
PubMed1999

Otomastoiditis caused by Rhodococcus equi in a patient with AIDS.

Rhodococcus equi is a well-recognized pathogen in veterinary medicine and a rare but well-documented cause of cavitary pneumonia in immunocompromised patients. Most cases of Rhodococcus equi infections in these patients involve the lungs. Otomastoiditis due to Rhodococcus equi is rare, and disseminated Rhodococcus equi with otomastoiditis has never been reported. We report a case of otomastoiditis with systemic dissemination due to Rhodococcus equi in a patient with AIDS.

AIDS-Related Opportunistic Infections↗
PubMed1999

Activation of protein kinase A increases phospholipase D activity and inhibits phospholipase D activation by acetylcholine in tracheal smooth muscle.

Increased cAMP by stimulation of adenylyl cyclase with forskolin or by beta-adrenoceptor activation with isoproterenol increased phospholipase D (PLD) activity in tracheal smooth muscle strips. PLD activity was measured by the accumulation of phosphatidylethanol. A linear increase in the concentration of phosphatidylethanol was observed over 20 min in muscle strips treated with either forskolin or isoproterenol. Cholinergic stimulation with acetylcholine (ACh), by contrast, caused a rapid increase in phosphatidylethanol followed by a slow decline in the concentration of phosphatidylethanol from 5 to 20 min in the continued presence of ACh. Concomitant treatment with ACh and either forskolin or isoproterenol eliminated the rapid increases in phosphatidylethanol associated with ACh treatment. The response to forskolin or isoproterenol was not influenced by ACh. Inhibition of protein kinase C with calphostin C or bisindolylmaleimide I had no effect on isoproterenol- or forskolin-stimulated PLD activity but inhibited ACh-activated PLD activity. Protein kinase A (PKA) inhibitors H-89 and KT5720 significantly decreased forskolin- and isoproterenol-mediated activation of PLD activity. PKA inhibition also eliminated inhibition of ACh-stimulated PLD activity by forskolin or isoproterenol. Activation of adenylyl cyclase by forskolin or by isoproterenol caused increased phosphorylation of phospholipase C-beta(2) isoform and reduced the formation of inositol phosphates after ACh stimulation of muscarinic receptors. These results suggest that increasing the concentration of cAMP activates PLD via activation of PKA and that the increased activity of PKA also inhibits cholinergic stimulation of PLD, in part at least by inhibiting the activation of phospholipase C by ACh.

Acetylcholine↗
PubMed1999

Compliance of the respiratory system as a predictor for successful extubation in very-low-birth-weight infants recovering from respiratory distress syndrome.

OBJECTIVE: To develop additional criteria to predict for successful extubation of very-low-birth-weight infants recovering from respiratory distress syndrome. DESIGN: Prospective study. SETTING: Neonatal intensive care unit at a university teaching hospital. INTERVENTIONS: Infants ready for extubation according to clinical, ventilatory and blood gas criteria were studied. Before extubation, tidal volume (Vt), minute ventilation, respiratory rate/Vt and mean inspiratory flow were measured during two different ventilatory settings: (i) during intermittent mandatory ventilation (IMV); and (ii) while breathing spontaneously with endotracheal continuous positive airway pressure (CPAP). Tidal volume was obtained through electronically integrated flow measured by a hot-wire anemometer. Total respiratory compliance (Crs) was determined during IMV and was derived from the formula Vt/PIP-PEEP, where the difference between peak inspiratory pressure (PIP) and positive end-expiratory pressure (PEEP) represented the ventilator inflation pressure. MEASUREMENTS AND MAIN RESULTS: Each of 49 infants was studied once before extubation. 33 infants (67%) were successfully extubated and 16 (32.6%) required reintubation. Infants in the success and failure groups were matched for gestation, post-conceptional age, study weight and methylxanthine therapy at the time of study. Successful extubation was associated with a higher mean absolute Crs value (ml/cm H2O) specific Crs value (standardised for body length; ml/cm H2O/cm) compared with infants in whom extubation failed (0.67 v. 0.46; P = 0.01 and 0.018 v. 0.014; P = 0.03, respectively). Analysis of ROC curves detected thresholds for Crs (0.5 ml/cm H2O) and Vt (7 ml) for predicting successful extubation. An absolute Crs value 0.5 ml/cm H2O or more improved the likelihood of successful extubation when compared with clinical/ventilator and blood gas criteria. The likelihood of successful extubation was 81% if the Crs value was > or = 0.5 ml/cm H2O. A tidal volume of 7 ml or more was less sensitive in contributing to successful extubation (sensitivity 69%). The major causes for extubation failure included atelectasis (diffuse and/or localised) and the presence of a patent ductus arteriosus. CONCLUSIONS: In addition to following very precise ventilatory criteria for extubation, we found that bedside measurement of total respiratory system compliance added to the likelihood of extubation success in infants recovering from respiratory distress syndrome. Prospective studies are needed to validate the findings of this study.

Aminophylline↗
PubMed1999

The patient's perception of chronic pain.

Chronic pain is common among hospital inpatients. Patients with chronic pain have low expectations of pain relief. The patient's need for information is frequently not met.

Acute Disease↗
PubMed1999

Gender aesthetics in the natural dentition.

This paper questions whether the size, position and angulation of upper anterior teeth 'reflect' the gender of a patient. Forty-six casts of natural teeth were given to 11 experts. The experts were asked to assess the gender of the patients. Overall the intra-observer agreement was fair (kappa = 0.33). Inter-observer agreement was fair (kappa = 0.23). On average 55% of casts taken from men were classified as 'male' and 55% of the casts taken from women were classified as 'female'. It is concluded, on the basis of this study, experts can not distinguish gender by the visual assessment of upper anterior teeth on casts alone.

Chi-Square Distribution↗
PubMed1998

Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates.

Marburg virus (MBGV), for which no vaccines or treatments currently exist, causes an acute hemorrhagic fever with a high mortality rate in humans. We previously showed that immunization with either killed MBGV or a glycoprotein (GP) subunit prevented lethal infection in guinea pigs. In the studies reported here, an RNA replicon, based upon Venezuelan equine encephalitis (VEE) virus, was used as a vaccine vector; the VEE structural genes were replaced by genes for MBGV GP, nucleoprotein (NP), VP40, VP35, VP30, or VP24. Guinea pigs were vaccinated with recombinant VEE replicons (packaged into VEE-like particles), inoculated with MBGV, and evaluated for viremia and survival. Results indicated that either GP or NP were protective antigens while VP35 afforded incomplete protection. As a more definitive test of vaccine efficacy, nonhuman primates (cynomolgus macaques) were inoculated with VEE replicons expressing MBGV GP and/or NP. Three monkeys received packaged control replicons (influenza HA); these died 9 or 10 days after challenge, with typical MBGV disease. MBGV NP afforded incomplete protection, sufficient to prevent death but not disease in two of three macaques. Three monkeys vaccinated with replicons which expressed MBGV GP, and three others vaccinated with both replicons that expressed GP or NP, remained aviremic and were completely protected from disease.

Animals↗
PubMed1998

Inefficient recognition of autologous viral sequences by intrahepatic hepatitis C virus-specific cytotoxic T lymphocytes in chronically infected subjects.

Cytotoxic T lymphocytes (CTL) capable of recognizing prototype hepatitis C virus (HCV) sequences have been shown to localize to the liver in chronically infected individuals, where they are thought to influence hepatic inflammation and viral replication. We isolated three intrahepatic CD8(+) CTL clones from two individuals with chronic HCV infection and compared the recognition of prototype and autologous HCV sequences. These CTL recognized epitopes within the NS2 (amino acids 957-964) or NS3 (amino acids 1402-1410 and 1406-1415) proteins in the context of HLA B37, B8, or A2.1, respectively. The corresponding predominant autologous HCV sequences (SDWAANGL, ELAAKLVGL, and ALRGMGVNAV, respectively) differed from the HCV-1 sequences used for screening (RDWAHNGL, ELAAKLVAL, and KLVALGINAV, respectively) at one to five residues. For each CTL clone, recognition of the autologous HCV sequence required significantly higher peptide concentrations than did recognition of the HCV-1 sequence; for two of the clones, recognition was minimal or absent at peptide concentrations as high as 25 microM. These data show that intrahepatic HCV-specific CD8(+) CTL clones can be relatively inefficient at recognizing autologous viral epitopes. Inefficient recognition of autologous HCV sequences should influence the interpretation of data generated using prototype HCV sequences and might have implications in vivo.

Amino Acid Sequence↗