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J Lloyd

Publications and source records attributed to J Lloyd.

At least 19 recordsLinked to original sources
PubMed1999

Serial phospholipid analysis in preterm infants: comparison of Exosurf and Survanta.

The initial clinical response to synthetic or natural surfactant is different and long-term complications from meta-analysis suggest that bronchopulmonary dysplasia and retinopathy of prematurity may be increased in infants given synthetic surfactant. It is possible that this is due to differences in the phospholipid composition of lung fluid following administration of these surfactants. Infants less than 32 weeks gestation with respiratory distress syndrome (RDS) were randomly assigned to receive either Exosurf, an artificial surfactant, or Survanta, a natural surfactant. Endotracheal or hypopharyngeal aspirates were obtained from these infants and from control infants who had normal lungs. The aspirates were taken prior to and up to 28 days following surfactant administration. The different phospholipids were separated by thin layer chromatography and expressed as a percent of total phospholipid measured. Infants with normal lungs had a higher proportion of phosphatidylcholine than those with RDS prior to treatment. The infants with normal lungs had a greater proportion of phosphatidylinositol in their lung aspirates than both treatment groups at 24 h. Infants in the Survanta group had a higher proportion of phosphatidylglycerol at 48 h than the group with normal lungs. No other differences were found in phospholipid composition up to 28 days. There were no major differences in the phospholipid profile in infants with RDS treated with either Exosurf or Survanta. In conclusion, neither the clinical differences initially seen between infants treated with either Exosurf or Survanta, nor the long-term outcome could be explained by the phospholipid composition of serial samples of lung aspirates.

Analysis of Variance↗
PubMed1998

Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Administration, Oral↗
PubMed1998

Cytological changes in endotracheal aspirates associated with chronic lung disease.

Endotracheal aspirates taken serially from mechanically ventilated premature infants born at < 28 weeks gestation between March 1992 and August 1993 were studied to determine whether early cytological changes would be a good predictor of lung damage in infants who develop chronic lung disease (CLD). CLD was diagnosed if the infant required supplemental oxygen at 36 weeks corrected gestational age. Fifty-five infants were enrolled in the study, five died and of the 50 infants remaining, 17 (34%) developed CLD. The infants with CLD had a significantly lower gestation (25.5 +/- 1.8 (mean +/- 1 SD) versus 26.2 +/- 0.9 weeks, p < 0.05), significantly more required surfactant (14/17 vs. 16/33, p < 0.05) and were ventilated for a significantly longer period (43.3 +/- 26.6 vs. 19.3 +/- 12.8 days, p < 0.0001). Endotracheal aspirate cytology showed that infants with CLD had significantly more degenerated columnar epithelial cells on day 3 (p = 0.001), and more neutrophils on day 10 (p = 0.007). Though not predictive of CLD, cytological changes consistent with bronchial epithelial and pulmonary damage followed by an inflammatory response were found in the tracheal aspirates of a group of infants clinically diagnosed with CLD.

Chronic Disease↗
PubMed1998

Interobserver reliability of the click test: a rapid bedside test to determine surfactant function.

OBJECTIVE: To determine the interobserver reliability of the click test, a rapid bedside test of surfactant function. METHODOLOGY: One hundred samples (48 amniotic fluid, 28 gastric aspirates, 24 tracheal aspirates) were obtained from pregnant women, term and preterm infants managed at two perinatal centres. Gestational ages of the pregnancies or infants at time of sampling ranged from 24 to 40 weeks (mean +/- s.d.: 31+/-5). The click test was performed independently by two observers, with differing levels of experience, and blinded to each other's results. Interobserver reliability was determined for samples classified as negative (no clicking bubbles), equivocal (a few clicking bubbles seen after 2 min of looking), and positive (clicking bubbles seen easily on first look). As negative and equivocal test results suggest surfactant dysfunction, these results were also combined to provide a dichotomised result. RESULTS: For samples classified as negative, equivocal and positive the interobserver agreement was 0.83, with agreement beyond chance shown by a quadratic weighted Kappa of 0.74 (95% CI = 0.62-0.86). When negative and equivocal results were combined, the simple Kappa was 0.73 (95% CI = 0.59-0.87). CONCLUSIONS: The click test has a high level of interobserver reliability. It is rapid, simple, accurate and able to be taught to medical and nursing staff with appropriate training. It has many potential applications including the prediction of fetal lung maturity in women with premature rupture of membranes, and in term and preterm infants who require the bedside testing of surfactant function.

Amniotic Fluid↗
PubMed1998

Non-Acanthamoeba amebic keratitis.

PURPOSE: To describe the clinical presentation and outcome of two cases with presumed non-Acanthamoeba amebic keratitis. METHODS: Case reports. RESULTS: Both patients presented with typical symptoms and signs of Acanthamoeba keratitis. The patients' soft contact lenses, lens cases, open solutions, and conjunctival samples were cultured. Diagnosis of non-Acanthamoeba amebic keratitis was based on the presence of keratitis and amebic growth from patients' contact lenses of the affected eyes. Amebic culture from the contralateral contact lens was negative. Vahlkampfia cysts were identified in case 1, and Naegleria cysts in case 2. Topical treatment with polyhexamethylene biguanide and propamidine resolved the keratitis in case 1. Case 2 was lost to follow-up. CONCLUSION: Non-Acanthamoeba amebic keratitis was diagnosed in two patients based on the clinical presentation (resembling Acanthamoeba keratitis), culture of the contact lens, and response to antiamebic treatment (in one case). Keratitis associated with Naegleria contamination of contact lenses has not been previously reported.

Adolescent↗
PubMed1998

Experiences with continuous infusion of recombinant activated factor VII.

A questionnaire was sent to 28 haemophilia treatment centres known to have used recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark), to collect data on continuous infusion of this product. This mode of administration was recently introduced for rFVIIa but there are several questions which remain to be answered in order to optimize this technique. Of the 26 responding centres, 14 had used rFVIIa in continuous infusion for 40 treatment episodes over a total of 283 days. In most of the cases the treatment was targeted at a factor VII level of 10 IU/ml, monitored by the one-stage clotting assay. This seemed to be adequate for most of the haemorrhagic and surgical procedures. Pretreatment pharmacokinetic evaluation was performed in only a minority of the cases but is probably of great importance given the wide variation observed in the clearance values. A strategy was necessary to prevent local thrombophlebitis, at least for infusions in peripheral veins; parallel infusion of heparin, saline or dextrose-saline proved effective. The question of optimal monitoring needs further attention. Haemorrhagic complications were significantly less frequent when treatment was combined with the antifibrinolytic tranexamic acid.

Drug Monitoring↗
PubMed1997

TLiSA1 (PTA1) activation antigen implicated in T cell differentiation and platelet activation is a member of the immunoglobulin superfamily exhibiting distinctive regulation of expression.

T lineage-specific activation antigen 1 (TLiSA1) antigen was initially described as a T lineage-specific activation antigen involved in the differentiation of human cytotoxic T cells. Subsequently, the antigen was identified on platelets and was shown to be involved in platelet activation, hence it was renamed platelet and T cell antigen 1 (PTA1), although identity between the two antigens was not established. In the present study we have cloned the cDNA encoding TLiSA1 from Jurkat cells and show it to be a novel member of the immunoglobulin superfamily with the unusual structure of two V domains only. Identity between TLiSA1 and platelet PTA1 is established by immunological criteria, by internal peptide sequences obtained from the purified platelet glycoprotein and by sequencing the platelet transcript after reverse transcriptase-polymerase chain reaction. In Jurkat cells, TLiSA1/PTA1 mRNA and surface protein expression is greatly stimulated by treatment of the cells with phorbol ester, but the T cell proliferative signal of phorbol ester and ionophore combined greatly reduces or abrogates this response, and this suppressive effect of the ionophore is not reversed by incorporating FK506 to inhibit calcineurin. Together with the known signaling role of PTA1, these data substantiate the notion that this molecule is implicated in T cell differentiation, perhaps by engagement of an adhesive ligand.

Amino Acid Sequence↗
PubMed1997

Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Nalt Acad Sci US 86:948-952, 1989). Two approaches were taken for new mutation detection; single-strand conformation polymorphism and sequencing to identify micro-mutations in the proximal promoter and exons 1-9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (delta1006-1007), a six nucleotide deletion in exon 8 (delta1441-1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS-B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence.

Adult↗
PubMed1997

Tardive tremor.

Explore the source record for details and available documents.

Anti-Dyskinesia Agents↗
PubMed1997

The AERX aerosol delivery system.

PURPOSE: We describe the AERX aerosol delivery system, a new, bolus inhalation device that is actuated at preprogrammed values of inspiratory flow rate and inhaled volume. We report on its in vitro characterization using a particular set of conditions used in pharmacokinetic and scintigraphic studies. METHODS: Multiple doses of aerosol were delivered from single use collapsible plastic containers containing liquid formulation. The aerosol was generated by forcing the formulation under pressure through an array of 2.5 micron holes. Air was drawn through the device at 70 LPM, and the aerosol was collected onto a filter or Andersen cascade impactor. The emitted dose was quantified from the filter collection data, and the particle size distribution was obtained from the best fit log-normal distribution to the impactor data. RESULTS: 57.0 +/- 5.9% of the dose of drug placed as an aqueous solution in the 45 microL collapsible container was delivered as an aerosol (n = 40). The best fit size distribution had an MMAD = (2.95 +/- 0.06) microns and a geometric standard deviation sigma g = 1.24 +/- 0.01 (n = 6). CONCLUSIONS: The AERX aerosol delivery system generates a nearly monodisperse aerosol with the properties required for efficient and repeatable drug delivery to the lung.

Administration, Inhalation↗
PubMed1997

Project to develop an autonomous practitioner programme.

The early 1990s has seen a rapid expansion in the nature of clinical roles in health care in response to a number of changes. Throughout 1996, The Oxford Radcliffe Hospital National Health Service (NHS) Trust, in partnership with Oxford Brookes University, School of Health Care, and the Royal College of Nursing (UK) have been collaborating to develop an educational programme at degree and masters level, to support new and evolving clinical roles in acute and primary care, across most professional health registration areas and clinical specialities. To ensure the proposed programme was 'fit for purpose'the Trust commissioned a Training Needs Analysis by the University of Birmingham and a Role Analysis by The Royal College of Nursing. Nurses and Midwives with expertise in practice, management, education and research, have collaborated to develop an innovative educational programme which enables a wide range of public and private health care professionals across acute and community settings to develop their autonomous practice. The programme is fully supported by development of policies which are appropriate to service delivery, support professional practice, multi-professional relationships, risk management and patient safety. The issue of contractual and professional responsibilities related to career development have been debated and a proactive strategy agreed. To ensure there is thorough evaluation of the area of practice, research projects to evaluate outcomes for patients as well as practitioners have been designed. This will additionally promote a culture of evidence-based practice.

Education, Nursing, Graduate↗
PubMed1997

A solitary benign lymphoid polyp of the rectum in a 51 year old woman.

A 51 year old woman presented with rectal bleeding from a mass lying just above the dentate line. Multiple biopsies were taken before the diagnosis of a benign lymphoid polyp was made. This is a rare condition that more commonly presents in children and poses a diagnostic challenge.

Diagnosis, Differential↗
PubMed1997

Development and validation of a particle-enhanced turbidimetric inhibition assay for urine albumin on the Dade aca analyzer.

The measurement of urine albumin now has a well-established role in the monitoring of patients with diabetes mellitus. We have developed a particle-enhanced immunoturbidimetric inhibition assay for urine albumin on the Dade aca analyzer. The inhibition approach removes any of the potential antigen excess difficulties that could be expected from the wide clinical range of urine albumin, but retains the sensitivity advantages of latex-enhanced immunoturbidimetry. Human serum albumin (HSA) is covalently attached to 40-nm poly(chloromethyl)styrene-modified latex particles. This reagent, along with monoclonal antibody to HSA, is aliquoted into the aca reagent pack along with polyethylene glycol 8000 in a tablet form (giving a final reaction concentration of 15 g/L). A 150 mmol/L phosphate buffer, pH 7.8, is used to fill the reagent pack in the instrument and the agglutination reaction is monitored at 340 nm. The sample volume is 100 microL and the calibration curve covers the range 2-250 mg/L. Evaluation of commercial scale reagents against the Beckman Array nephelometric immunoassay system gave a Deming regression correlation of aca = 0.87 x Beckman + 8.5, r = 0.995, n = 145. Mean analytical recovery was 104+/-4.5%, n = 20, and there was no evidence of a lack of parallelism. Interassay precision was 8.8% at 10.0 mg/L and <2.5% at >65 mg/L. Calibrator stability was in excess of 60 days. A small reference range study (24-h urine collections, n = 27) gave a mean of 5.6 mg/L with a range of 0.5-16.2 mg/L. Analytical sensitivity (2.5 SD from zero) was 0.40 mg/L.

Albuminuria↗
PubMed1996

Phenotypic variation in Waardenburg syndrome: mutational heterogeneity, modifier genes or polygenic background?

We have identified 11 mutational changes in the PAX3 gene in patients with type 1 Waardenburg syndrome (WS1) including three in the paired domain, six within or immediately adjacent to the homeodomain and two previously described polymorphic variants in exons 2 and 6. The affected members of one family carried substitutions involving two base pairs separated by one unaltered codon. Two of the deleterious mutations were identical and three others were identical to previously reported mutations. A comparison of clinical findings in families carrying substitutions in the same codon failed to reveal conspicuous similarities. Although subtle mutation-specific effects may well exist, allelic heterogeneity clearly cannot account for within family variation. However, the striking concordance of a pair of monozygotic twins with Waardenburg syndrome (WS) and previous reports of similar pairs indicate that phenotypic variation in WS has a genetic basis. If the genetic effects are mediated by oligogenic epistasis, as studies in the mouse suggest, it may ultimately be possible to predict clinically relevant aspects of the Waardenburg phenotype.

Amino Acid Sequence↗