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C A Hart

Publications and source records attributed to C A Hart.

At least 127 records · Page 7Linked to original sources
PubMed2000

Performance characteristics of the polymerase chain reaction assay to confirm clinical meningococcal disease.

BACKGROUND: Confirmation of clinical meningococcal disease (MCD) is essential for management of patients, contacts, and outbreaks. Blood and CSF cultures, the traditional gold standard diagnostic tests, have been adversely affected by preadmission parenteral penicillin and fewer lumbar punctures. Rapid, reliable serogroup determination without the need to grow isolates could improve laboratory confirmation of MCD. AIMS: To determine performance characteristics of the currently available meningococcal polymerase chain reaction (PCR) assays in a clinical setting. METHODS: Prospective study of 319 children presenting with a suspected diagnosis of MCD (fever and a rash, or suspected bacterial meningitis) over a 16 month period. RESULTS: A total of 166 (52% of all) children had clinical MCD: diagnosis was confirmed microbiologically in 119 (72%) of these. Performance characteristics (sensitivity, specificity, negative predictive value, positive predictive value) in confirmation of clinical MCD were respectively (95% confidence interval): blood culture 31% (24-38%), 100%, 57% (49-65%), 100%; blood PCR 47% (39-55%), 100%, 65% (58-73%), 100%; any test positive 72% (65-79%), 100%, 77% (70-84%), 100%. CONCLUSIONS: Meningococcal DNA detection in blood or CSF by PCR is a useful method of diagnosis of MCD. PCR of peripheral blood performs better than blood culture. In a child with clinically suspected MCD, PCR assays, bacterial antigen tests, and oropharyngeal swabbing for meningococcal carriage should be performed in addition to blood or CSF culture, to improve case confirmation.

Antigens, Bacterial↗
PubMed2000

Hypocalcaemia in severe meningococcal infections.

AIM: To determine the incidence of hypocalcaemia in critically ill children with meningococcal disease. METHODS: In a prospective cohort study, 70 of 80 patients admitted consecutively with a clinical diagnosis of meningococcal disease to intensive care had measurements of total and ionised calcium on admission. Parathormone and calcitonin were measured in a proportion of the children. RESULTS: Total and ionised calcium concentrations were low in 70% of the children. There was a weak relation of calcium concentration to the volume of blood derived colloid which had been given, but a good relation to disease severity, where sicker children had lower calcium concentrations. Although the parathormone concentration was higher in children with lower calcium concentrations, some children had low ionised calcium concentrations, without an increase of parathormone concentration. Serum calcitonin concentration was not related to calcium concentrations. CONCLUSION: Hypocalcaemia is common in meningococcal disease.

Calcitonin↗
PubMed2000

Human herpesviruses in the cornea.

AIMS: To determine the sensitivity and specificity of culture, immunohistochemistry (IHC), the polymerase chain reaction (PCR), and in situ hybridisation (ISH) for detecting herpes simplex virus (HSV-1) in the cornea of patients undergoing penetrating keratoplasty. To compare the incidence of HSV-1 in the cornea with that of varicella zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). METHODS: The corneas of 110 patients, 52 with a documented history of herpes keratitis (HSK) and 58 with non-herpetic corneal disease, were investigated using IHC, PCR, ISH, and culture. RESULTS: HSV-1 DNA and antigen were detected in 82% and 74% respectively, of corneas of patients with HSK and in 22% and 15% of corneas of patients with no history of HSK. The sensitivity of PCR and IHC was 82% and 74% with a specificity of 78% and 85%, respectively. HSV-1 DNA and antigen were found more frequently and in increased amounts in corneas of patients with a short interval between their last attack of HSK and surgery. There was a good correlation between PCR and IHC in 71%. HSV-1 was isolated by culture in 2%. Latency associated transcripts were not detected using ISH. Evidence of VZV DNA or antigen was found significantly more frequently in the corneas of patients with a history of HSK (p<0.001). No evidence of EBV or CMV was found in any cornea. CONCLUSIONS: PCR and IHC are both sensitive for the detection of HSV-1 in the cornea. A combination of PCR and IHC increases the specificity for the diagnosis of HSK to 97%. HSV-1 appears to be slowly removed from the cornea. VZV and HSV-1 may co-infect the cornea.

Carrier State↗
PubMed2000

Diarrhoeal disease.

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Bacterial Infections↗
PubMed2000

Correlation between intracellular pharmacological activation of nucleoside analogues and HIV suppression in vitro.

Following intracellular activation of HIV nucleoside analogue reverse transcriptase inhibitors, their triphosphates (ddNTPs) compete with endogenous nucleoside triphosphates (dNTPs) for incorporation into proviral DNA. In this study we have examined the effect of combinations of two thymidine analogues, stavudine (d4T) and zidovudine (ZDV), and two cytidine analogues, lamivudine (3TC) and zalcitabine (ddC) on intracellular drug activation and on the relevant competing dNTP in uninfected and persistently HIV-infected cells. Endogenous triphosphates of deoxycytidine (dCTP) and deoxythymidine (dTTP) were measured using a template primer assay and the ratio of ddNTP:dNTP was calculated. Antiviral activity of two-drug combinations was also assayed by p24 ELISA. A significant reduction in d4T triphosphate (d4TTP) [0.11+/-0.09 pmol/10(6) cells to undetectable (<0.01); P=0.039] in the presence of equimolar concentrations of ZDV and d4T, resulted in a decrease in the d4TTP/dTTP ratio of 90%. ZDVTP/dTTP was not significantly altered in the presence of d4T. 3TC (10 microM) reduced total ddC phosphates by 57% and ddCTP/dCTP by 27%. 3TC phosphorylation was comparatively unaffected by ddC, up to a concentration of 10 microM ddC (>100 times the plasma concentration achieved following standard dosing). 3TC plus ddC resulted in greater p24 inhibition than 3TC or ddC alone (P<0.001). Combining one thymidine analogue (ZDV or d4T) with one cytidine analogue (3TC or ddC) resulted in greater inhibition of p24 inhibition than with any single agent. From a pharmacological viewpoint, the combination of ZDV plus d4T should be avoided, but in vitro the combination of 3TC plus ddC confers modest benefit over either drug alone. This in vitro study illustrates that decreases in ddNTP/dNTP are consistent with a reduction in antiviral effect.

Anti-HIV Agents↗
PubMed1999

Prevalence and risk factors for feline Bordetella bronchiseptica infection.

A cross-sectional survey of a convenience-sample of 740 cats was undertaken to obtain an estimate of the prevalence of Bordetella bronchiseptica infection, and to identify risk factors that might predispose them to the infection. Data on individual cats and household variables, including disease status and animal contacts were obtained by questionnaire. B bronchiseptica was isolated from 82 (11 per cent) of the cats sampled. The prevalence of B bronchiseptica varied with the type of household sampled, being 19.5 per cent in rescue catteries, 9 per cent in breeding catteries, 13.5 per cent in research colonies, and 0 per cent in household pets. On the basis of a univariable analysis, 19 of 29 predictor variables were found to be significantly associated with the isolation of B bronchiseptica, including an association with cats in rescue catteries, and with cats from premises with larger numbers of animals. Separate analysis of the rescue cattery subpopulation showed a highly significant association on multivariable analysis with current respiratory disease, suggesting that different risk factors may operate in this type of environment. In the whole sample there was also strong association with cats from households containing a dog with recent respiratory tract disease. The clinical signs observed in the B bronchiseptica-positive cats included sneezing, ocular and nasal discharges and coughing, although only the association with sneezing was statistically significant. There was no significant association between the isolation of B bronchiseptica and the isolation of respiratory viruses, suggesting that in some circumstances B bronchiseptica may be able to cause disease independently.

Analysis of Variance↗
PubMed1999

Regulation of neutrophil FcgammaRIIIb (CD16) surface expression following delayed apoptosis in response to GM-CSF and sodium butyrate.

When neutrophils undergo apoptosis, they lose expression of the surface receptor CD16 (FcgammaRIIIb). Thus levels of surface CD16 are good indicators of apoptotic or non-apoptotic neutrophils. Shedding of CD16 occurs via the activity of a metalloproteinase that cleaves the receptor from the plasma membrane. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and sodium butyrate both stimulate neutrophil gene expression, protect these cells from apoptosis, and maintain expression of surface CD16. In this report we have investigated whether these agents maintain surface expression of CD16 via (1) decreased shedding (2) increased mobilization of the internal pool of pre-formed CD16, or (3) via de novo biosynthesis of new receptor molecules. Although GM-CSF and sodium butyrate both preserved surface expression of CD16, GM-CSF actually accelerated the rate of shedding of this receptor. Maintenance of surface levels was achieved by substantial mobilization of the internal pool of CD16. Sodium butyrate, on the other hand, maintained surface expression without extensive store depletion via a mechanism that appeared to involve a decreased rate of shedding. In these experiments we could find no evidence for de novo biosynthesis of CD16 stimulated by either GM-CSF or sodium butyrate. These experiments indicate that multiple mechanisms exist for the maintenance of surface CD16 during rescue of neutrophils from apoptosis by different agents.

Apoptosis↗
PubMed1999

Human serum beta2-microglobulin levels: correlation with total serum IgG and placental IgG transfer in HIV-infected and non-HIV infected individuals.

The acquisition of maternal immunoglobulin G (IgG) is fundamental to the immune defence of the neonate. The receptor responsible for IgG transfer across the human placenta has also been implicated in the maintenance of IgG levels in the circulation. beta2-microglobulin is part of the Fc receptor (FcR) that has recently been purified from the human placenta. In HIV infection, increasing serum levels of total IgG and beta2-microglobulin are observed as the disease progresses. Herein, we have investigated the correlation between beta2-microglobulin and total serum IgG levels in HIV-seropositive mothers and their term neonates (HIV group, n = 37), as well as in HIV-seronegative mothers and their term neonates (control group, n = 50). Serum maternal beta2-microglobulin was directly correlated with total serum IgG levels in HIV-infected mothers (r = 0.58; P = 0.0002), but not in healthy HIV-seronegative mothers (r = -0.20; P = 0.16). Maternal serum beta2-microglobulin was also inversely correlated with placental antibody transfer of total IgG in mother-newborn pairs from the HIV group (r = 0.38; P = 0.02), but not from the control group (r = 0.15. P = 0.31). These results seem to indicate that, in HIV infection, elevated serum beta2-microglobulin levels could be involved in maintenance of abnormally high total serum IgG concentrations; by interfering with the binding of IgG to Fc receptors at the maternal-fetal interface, they might also reduce IgG transfer. By contrast, in normal non-HIV infected individuals, serum beta2-microglobulin levels do not appear implicated in regulation of these two phenomena.

Adult↗
PubMed1999

Hantavirus infections: epidemiology and pathogenesis.

Hantaviruses are enveloped RNA viruses that persistently infect rodent hosts without ill-effect. The host persistently excretes virus in urine and saliva. Man becomes infected from the rodents when one enters the ecological niche of the other. There are two major clinical presentations--haemorrhagic fever with renal syndrome, found worldwide in various forms and hantavirus pulmonary syndrome, found only in the Americas. This review examines the virology, epidemiology and pathogenesis of these emerging pathogens.

Animals↗
PubMed1999

Systemic absorption of gentamicin in the management of active mucosal chronic otitis media.

A prospective study was performed on patients with active mucosal chronic otitis media who were being treated with the gentamicin-containing preparation Gentisone HC. In 27 patients plasma gentamicin levels were measured. Detectable levels were found in 7/27 (26%). Pre- and post-treatment audiometry was performed on 16 patients. There was no statistically significant difference in the change of the mean bone conduction thresholds as a result of treatment, between the treatment and control ears (P = 0.07, Wilcoxon signed Ranks Test at 95% C.I.). We conclude that there is evidence of systemic absorption of gentamicin that would ultimately be absorbed into the perilymph. Gentamicin is known to be ototoxic affecting the vestibular system in lower doses and the cochlea in high doses, hence audiometric assessment is not an appropriate screen for ototoxicity when using topical gentamicin-containing drops. Alternative topical preparations should be further investigated.

Absorption↗
PubMed1999

Ecdysone agonist inducible transcription in transgenic tobacco plants.

A novel chemical-induced gene regulatory system for plants consisting of two molecular components is described. The first, or regulatory, cassette comprises a chimeric receptor composed of the hinge and ligand binding domains of the Heliothis virescens ecdysone receptor and the transactivation domain of the Herpes simplex VP16 protein fused to the DNA binding domain and transactivation of a mammalian glucocorticoid receptor. The second component, a reporter cassette, contains six copies of the glucocorticoid response element (GRE) fused to the minimal 35SCaMV promoter and beta-glucuronidase. The system uses a commercially available non-steroidal ecdysone agonist, RH5992 (tebufenozide), as an inducer. Activation of gene expression is shown in both tobacco transient protoplasts and transgenic plants. The response is ligand dependent and is modulated by the change in minimal promoter context. The system is capable of inducing transgene activity up to 420-fold corresponding to 150% of the activity observed with positive controls (35SCaMV:GUS).

Base Sequence↗