Search PubMed⌕ Search

Biomedical subjects

J Lloyd

Publications and source records attributed to J Lloyd.

At least 19 recordsLinked to original sources
PubMed2000

Experience with continuous infusion of recombinant activated factor VII in the Asia-Pacific region.

There is increasing interest in continuous infusion of recombinant activated factor VII (rFVIIa) as a convenient and safe alternative to intermittent bolus therapy. In the Australian patients reported in this paper, cost savings of up to 25% in the first 12 h of treatment with continuous infusion of rFVIIa have been achieved safely, suggesting that substantial overall savings are possible. However, in the Thai patient reported, a dose reduction of 35% in the first 12 h was associated with poor haemostatic control, suggesting that a dose reduction of >25% may be inadvisable. The indications for treatment in the five Australian patients were: retroperitoneal haemorrhage (n = 3); right forearm compartment syndrome (n = 1); wrist haemarthrosis and median nerve compression (n = 2); sublingual haematoma (n = 1); and cerebral (mid-brain) haemorrhage (n = 1). Treatment was effective in four out of five patients (six bleeding episodes) and there was one treatment failure where treatment had been substantially delayed. The Thai patient was treated as part of a prospective, uncontrolled, observational study of 34 bleeding episodes in 22 patients in the Asia-Pacific region. Treatment was judged ineffective after 24 h, but full haemostatic control was subsequently achieved with intermittent rFVIIa therapy.

Adult↗
PubMed1999

The pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells from patients infected with HIV-1.

OBJECTIVE: To assess the pharmacokinetics of lamivudine phosphorylation in peripheral blood mononuclear cells (PBMC) from patients infected with HIV-1. DESIGN: Single-center, open-label, randomized, two-period, cross-over study in 10 asymptomatic, antiretroviral-experienced, HIV-1-infected patients who had a CD4+ lymphocyte count of 200-500 x 10(6)/l and had received combination treatment with lamivudine 150 mg twice a day plus zidovudine 600 mg a day (divided into two or three doses) for > or = 16 weeks prior to study entry. METHODS: Patients were randomly assigned to receive lamivudine 150 mg twice a day or lamivudine 300 mg twice a day for 14 days, with at least a 48-h washout period between treatments. Serial blood samples were collected over 36 h for determination of lamivudine serum concentrations using liquid chromatography/mass spectrometry and intracellular phosphate PBMC concentrations using high performance liquid chromatography/radioimmunoassay methods. Pharmacokinetic parameters were calculated based on lamivudine and lamivudine anabolite concentration-time data. RESULTS: Intracellular pharmacokinetic parameters were highly variable between patients (coefficient of variations approximately 50%). The two regimens produced lamivudine-total phosphate (totP) values of a similar magnitude. Although the 300-mg regimen tended to produce higher lamivudine-monophosphate (MP) and -triphosphate (TP) values, differences from values produced by the 150-mg regimen were not statistically significant. As lamivudine diphosphate (DP) was the predominant anabolite, accounting for 50-55% of lamivudine-totP (compared with 30-35% for lamivudine-MP and 15-20% for lamivudine-TP), the conversion of lamivudine-DP to lamivudine-TP can be regarded as the rate-limiting step. The median lamivudine-TP intracellular half-life (t1/2) for the 150-mg and 300-mg regimens did not differ significantly (15.3 and 16.1 h, respectively). Serum lamivudine pharmacokinetic parameters were consistent with those observed in previous studies in HIV-1-infected patients. No apparent linear relationships were observed between lamivudine intracellular anabolite and serum data. CONCLUSIONS: The intracellular pharmacokinetics of lamivudine phosphorylation in PBMC from asymptomatic HIV-1-infected patients are highly variable and do not differ statistically between the 150- and 300-mg twice a day regimens. The variations in intracellular lamivudine-TP concentrations following these two lamivudine dosage regimens are unlikely to result in differences in clinical effect. This was confirmed by the results of a large phase III study in HIV-1-infected patients which showed no differences in HIV-1 RNA or CD4+ lymphocyte counts between the 150- and 300-mg lamivudine regimens in combination with zidovudine.

Anti-HIV Agents↗
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↗
PubMed1999

Kikuchi-Fujimoto's syndrome masquerading as tuberculosis.

We report a case of a 27-year-old Asian man presenting with the typical features of tuberculous cervical lymphadenitis who was commenced on anti-tuberculous therapy on the strength of the clinical presentation. Histological examination of an excised cervical lymph node however, revealed the diagnosis of Kikuchi's syndrome; a histiocytic necrotizing lymphadenitis which is usually self-limiting.

Adult↗
PubMed1999

Extension of extramammary Paget disease of the vulva to the cervix.

Extramammary Paget disease of the vulva was found in association with vulval adenocarcinoma in an elderly woman who also had a uterine prolapse. The characteristic histological appearances of extramammary Paget disease were masked by striking reactive changes in the squamous epithelium. Primary excision of both the intraepithelial and invasive disease appeared complete. However, a subsequent hysterectomy with repair of the prolapse revealed extramammary Paget disease in the upper vaginal mucosa and cervix, a finding which is very rarely described. Pathogenesis and diagnosis of extramammary Paget disease is discussed, with differential diagnosis and reference to immunohistochemical methods.

Adenocarcinoma↗
PubMed1999

Dietary considerations in osteopenia in tube-fed nonambulatory children with cerebral palsy.

Children with nonambulatory cerebral palsy are frequently found to be osteopenic. We sought factors, in addition to immobility and anticonvulsant therapy, that may contribute to the osteopenia. A retrospective chart review of 19 children with nonambulatory cerebral palsy who received gastrostomy tube feedings of standard commercial formulas was performed. Less than 75% of the Recommended Daily Allowance (RDA) was administered to 95% of the children for calories, 58% for calcium, 68% for phosphorus, and 74% for vitamin D. Five of the 19 children sustained fractures without major trauma. This study suggests that inadequate intake of crucial vitamins and minerals may contribute to the severe osteopenia observed in many children with nonambulatory cerebral palsy. The nutritional needs of these children, including those for micronutrients, must be defined and appropriate supplementation given.

Adolescent↗
PubMed1999

Unsafe injections in the developing world and transmission of bloodborne pathogens: a review.

Unsafe injections are suspected to occur routinely in developing countries. We carried out a literature review to quantify the prevalence of unsafe injections and to assess the disease burden of bloodborne infections attributable to this practice. Quantitative information on injection use and unsafe injections (defined as the reuse of syringe or needle between patients without sterilization) was obtained by reviewing the published literature and unpublished WHO reports. The transmissibility of hepatitis B and C viruses and human immunodeficiency virus (HIV) was estimated using data from studies of needle-stick injuries. Finally, all epidemiological studies that linked unsafe injections and bloodborne infections were evaluated to assess the attributable burden of bloodborne infections. It was estimated that each person in the developing world receives 1.5 injections per year on average. However, institutionalized children, and children and adults who are ill or hospitalized, including those infected with HIV, are often exposed to 10-100 times as many injections. An average of 95% of all injections are therapeutic, the majority of which were judged to be unnecessary. At least 50% of injections were unsafe in 14 of 19 countries (representing five developing world regions) for which data were available. Eighteen studies reported a convincing link between unsafe injections and the transmission of hepatitis B and C, HIV, Ebola and Lassa virus infections and malaria. Five studies attributed 20-80% of all new hepatitis B infections to unsafe injections, while three implicated unsafe injections as a major mode of transmission of hepatitis C. In conclusion, unsafe injections occur routinely in most developing world regions, implying a significant potential for the transmission of any bloodborne pathogen. Unsafe injections currently account for a significant proportion of all new hepatitis B and C infections. This situation needs to be addressed immediately, as a political and policy issue, with responsibilities clearly defined at the global, country and community levels.

Adult↗
PubMed1999

Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates.

Thousands of millions of injections are delivered every year in developing countries, many of them unsafe, and the transmission of certain bloodborne pathogens via this route is thought to be a major public health problem. In this article we report global and regional estimates of the number of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections that may occur from unsafe injections in the developing world. The estimates were determined using quantitative data on unsafe injection practices, transmission efficiency and disease burden of HBV, HCV and HIV and the prevalence of injection use obtained from a review of the literature. A simple mass-action model was used consisting of a generalized linear equation with variables accounting for the prevalence of a pathogen in a population, susceptibility of a population, transmission efficiency of the pathogen, proportion of injections that are unsafe, and the number of injections received. The model was applied to world census data to generate conservative estimates of incidence of transmission of bloodborne pathogens that may be attributable to unsafe injections. The model suggests that approximately 8-16 million HBV, 2.3-4.7 million HCV and 80,000-160,000 HIV infections may result every year from unsafe injections. The estimated range for HBV infections is in accordance with several epidemiological studies that attributed at least 20% of all new HBV infections to unsafe injections in developing countries. Our results suggest that unsafe injections may lead to a high number of infections with bloodborne pathogens. A major initiative is therefore needed to improve injection safety and decrease injection overuse in many countries.

Cross Infection↗
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↗