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Biomedical subjects

N French

Publications and source records attributed to N French.

At least 37 records · Page 2Linked to original sources

The immune response to Mycobacterium tuberculosis in HIV-infected and uninfected adults in Uganda: application of a whole blood cytokine assay in an epidemiological study.

SETTING: Out-patient clinic, Entebbe, Uganda. BACKGROUND: It has been proposed that 'type 1' cytokines are essential in protective immunity to Mycobacterium tuberculosis and that suppression of 'type 1' or a switch to a 'type 2' profile is deleterious. We employed a simple assay to examine whether the dependence of the immunological responses to mycobacterial antigens on a range of explanatory factors could be determined in a population where tuberculosis is endemic. OBJECTIVE: To determine the relationship between the tuberculin skin test response and cytokine profile, and the effect of human immunodeficiency virus (HIV) infection. DESIGN: A cross-sectional study of 97 Ugandan adults (22 HIV-positive, 75 HIV-negative). Whole blood was stimulated in vitro using mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). 'Type 1' cytokines (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]), 'type 2' cytokines (IL-5 and IL-10) and tumour necrosis factor alpha (TNF-alpha) were measured in culture supernatants. RESULTS: Among HIV-negative subjects, a positive tuberculin skin test was associated with type 1 or mixed (type 1 + type 2) cytokine production, but a positive IFN-gamma response also occurred in a proportion of tuberculin skin test negative subjects (36% for PPD, 17% for CFP). In association with HIV infection, IFN-gamma responses to mycobacterial antigens were profoundly impaired (odds ratio [OR] 0.10 for PPD, 0.06 for CFP, P< or =0.001), but production of IL-2, IL-5 and TNF-alpha was relatively sustained, and IL-10 increased or sustained (OR 3.97 for PPD, P = 0.01, 1.14 for CFP, P = 0.99). CONCLUSION: The type 1/type 2 cytokine balance was not defined by the tuberculin skin test response, and may have a closer relation to protective immunity. IFN-gamma production was strikingly impaired in association with HIV infection, while production of type 2 cytokines was sustained or increased. Use of a simple assay allowed a large sample of subjects to be examined, producing epidemiologically meaningful results.

Adolescent↗

Pneumococcal vaccination in HIV-1-infected adults in Uganda: humoral response and two vaccine failures.

OBJECTIVES: To assess the feasibility of establishing a pneumococcal vaccine trial among HIV-1-infected adults in Uganda and to characterize their responses to 23-valent pneumococcal polysaccharide vaccine. DESIGN: An open-label pilot trial to assess recruitment and compliance of HIV-1-infected adults in Uganda to vaccination and to determine the immunogenicity of the vaccine. SETTING: A community clinic for HIV-1-infected adults in Entebbe, Uganda. METHODS: Levels of capsule-specific IgG to four common vaccine capsular serotypes were measured before vaccination and 1 month after vaccination. Subsequent rates of disease episodes and deaths, and immunologic responses in two vaccine failures, were followed. RESULTS: One month after-vaccination, both HIV-1-infected (n = 77) and seronegative control subjects (n = 10) demonstrated a significant rise in capsule-specific immunoglobulin G (IgG) for three of four serotypes tested, but levels were significantly lower among HIV-1-infected patients. In 149 patient-years of follow-up, two (2.6%) developed pneumococcal pneumonia, one bacteremic with serotype 1 and one non-bacteremic with serotype 13, a non-vaccine serotype; both patients showed inadequate killing of the organism in vitro. In this same follow-up period, 29 (38%) patients died. CONCLUSION: HIV-1-infected adults in Uganda are at high risk of pneumococcal disease and show a significant but suboptimal response to pneumococcal vaccine. Although reliable recruitment and follow-up of vaccinees is feasible, evaluation of vaccine efficacy may be compromised by limited responses to common vaccine serotypes, an unknown incidence of disease with non-vaccine serotypes, and a high rate of mortality unrelated to Streptococcus pneumoniae infection.

AIDS-Related Opportunistic Infections↗

Cross-clade recognition of p55 by cytotoxic T lymphocytes in HIV-1 infection.

OBJECTIVES: To evaluate cross-clade recognition of p55 antigen by cytotoxic T lymphocytes (CTL) in persons infected with diverse clades of HIV-1; to facilitate the development of a CTL-inducing vaccine to prevent transmission of multiple clades of HIV-1. DESIGN: Experiments were designed to evaluate whether persons in Uganda and the United Kingdom, infected with diverse clades of HIV-1, have CTL capable of recognizing and killing autologous target cells infected with recombinant vaccinia viruses (rVV) expressing the Gag protein from A, B, C and D clade HIV-1. The extent of cross-reactivity within such individuals, each infected with characterized virus, might reflect the type of cross-reactive immune response inducible by a monovalent vaccine. METHODS: Asymptomatic HIV-positive individuals were fully tissue-typed by ARMS (amplification of refractory mutation system) polymerase chain reaction. rVV expressing the Gag protein from identified A, B, C and D viruses were prepared. CTL were cultured and tested for cytolytic activity on autologous rVV-infected or peptide-pulsed B cells. RESULTS: Ugandan patients had inducible CTL responses recognizing A, B, C and D clade HIV-1 Gag. The majority of UK patients had inducible CTL responses that recognized two or more clades. No patient showed any HIV-2 cross-reactivity. Cross-reactive responses were characterized in three Ugandan patients. CONCLUSIONS: Most patients tested mounted cross-reactive CTL responses that recognized Gag proteins from clades of HIV-1 other than those with which they were infected.

Amino Acid Sequence↗

The incidence of sheep strike by Lucilia sericata on sheep farms in Britain: a simulation model.

Using a combination of a temperature-dependent simulation of the population dynamics of Lucilia sericata and a logistic model of sheep susceptibility, based on patterns of faecal soiling, fleece length and fleece humidity, a deterministic simulation model has been constructed to predict the incidence of sheep strike by L. sericata on lambs and ewes in Britain. Strikes are assigned to individual sheep in the flock according to a negative binomial distribution. The model shows that the majority of the first strikes of the season occur equally on ewes and lambs, when ewe fleeces are long and before lamb susceptibility increases though faecal soiling. With each subsequent generation of gravid blowflies, however, a greater proportion of strikes occur on lambs, while the number of strikes observed on ewes remains relatively consistent throughout the season. The increase in strike of lambs is due to the seasonal increase in lamb faecal soiling, associated with rising helminth infections and lamb fleece growth. The model shows that at the beginning of the season the incidence of strike is limited by the low number of flies present: towards the end of seasons, however, the blowfly population had grown large enough for the number of strikes to be limited by the number of susceptible ewes and lambs. The model shows that the seasonal incidence of strike is highly sensitive to the interactions between temperature, rainfall and would length. Strike was most prevalent under warm, wet conditions. However, there is a critical period during spring, where the short fleeces of lambs and ewes, in the latter case due to shearing, results in the desiccation of egg batches. If this coincides with dry conditions, the high levels of mortality result in suppression of the fly population and a reduction in the subsequent incidence of strike.

Animals↗

Antenatal steroids, condition at birth and respiratory morbidity and mortality in very preterm infants.

AIMS: To investigate (1) perinatal factors affecting condition at birth in very preterm infants (23-32 weeks) and (2) the relationship between poor condition at birth and neonatal respiratory morbidity and mortality. METHODOLOGY: Convenience sample (n = 479) drawn from a geographic population inception cohort. RESULTS: Antenatal steroid use reduced the risk of pH < or = 7.20 [Adjusted Odds Ratio 0.29 (95% CI 0.17, 0.50)], one minute Apgar < 4 [0.54 (0.33, 0.88)], and 5 min Apgar < 7 [0.44 (0.23, 0.84)]. Gestational age was significantly related to Apgar score but not cord arterial acid-base status. No other perinatal factor was significant. Poor condition at birth was associated with an increase in the incidence and severity of hyaline membrane disease and death. These effects were lessened in those exposed to steroids. CONCLUSION: Antenatal steroid use is associated with improved condition at birth and reduces the deleterious effects of poor condition at birth on early respiratory morbidity and mortality.

Acid-Base Equilibrium↗

Very preterm birth--a regional study. Part 1: Maternal and obstetric factors.

OBJECTIVE: To ascertain the demographic, pregnancy and obstetric factors associated with the delivery of a liveborn very preterm infant ( < 33 weeks of gestation) and to investigate any differences in these factors between identifiable aetiological groups. DESIGN: Cohort analytical study. SETTING: King Edward Memorial Hospital for Women (KEMH), Western Australia. MAIN VARIABLES EXAMINED: Maternal demographic and obstetric history, primary complication associated with delivery, obstetric management and mode of delivery. RESULTS: Six hundred and eight women who were delivered of 693 liveborn very preterm infants in Western Australia between 1.1.90 and 31.12.91, representing 1.22% of all women who were delivered of a liveborn infant in those years. Singleton pregnancy occurred in 517 (85%) and 541 (89%) were delivered in KEMH. Mean maternal age was 28 years with an excess of mothers less than 20 years of age and older than 34 years compared with the statewide perinatal data. Pre-eclampsia (n = 128, 21.1%), preterm prelabour rupture of membranes (n = 148, 24.3%), idiopathic preterm labour (n = 195, 30.4%) and antepartum haemorrhage (n = 111, 18.3%) were associated with 94.1% of deliveries. These proportions varied with plurality and period of gestation. Demographic details, use of antenatal steroids, exposure to labour and caesarean section delivery differed between mothers depending on the primary complication. Overall 322 (53.0%) received antenatal steroids and 297 (48.8%) were delivered by caesarean section. Factors associated with decreased use of steroids were gestational age of less than 27 weeks (odds ratio (OR) 0.54; 95% CI 0.36-0.83), preterm prelabour rupture of the membranes (OR 0.48; 95% CI 0.29-0.78) and idiopathic preterm labour (OR 0.56; 95% CI 0.35-0.91). Factors associated with increased use of steroids were multiple pregnancy (OR 1.70; 95% CI 1.02-2.81) and pre-eclampsia (OR 1.87; 95% CI 1.09-3.19). CONCLUSIONS: These very preterm deliveries account for only a small proportion of all deliveries. There are differences in the mother's demographic history, obstetric management and delivery depending on the primary aetiological factor.

Adult↗

Very preterm birth--a regional study. Part 2: The very preterm infant.

OBJECTIVE: To ascertain the growth characteristics, delivery room management and hospital mortality of very preterm liveborn infants (< 33 weeks of gestation) and to identify differences between infants associated with the aetiological factor related to their very preterm delivery. DESIGN: Cohort analytical study. SETTING: King Edward Memorial Hospital for Women, Western Australia. MAIN VARIABLES EXAMINED: Gestational age, birthweight, birthweight ratio, condition at birth and mortality. RESULTS: Six hundred and ninety-three liveborn very preterm infants were born to 608 mothers between 1.1.90 and 31.12.91. This was 1.37% of all liveborns in Western Australia. Three hundred and eighty-five (55.6%) were male. Growth characteristics (birthweight, birthweight ratio and proportion small for gestational age) differed between infants depending on the primary obstetric complication associated with the very preterm delivery. Overall 217 (31%) infants were small for gestational age, 34(4.9%) had a congenital anomaly, and 102 (14.7%) died. Corrected mortality, excluding major fatal congenital anomaly, was 86 (12.7%). The majority of infants died on the first day (n = 59 (57.8%)). The only factors associated with an increased or decreased mortality were decreasing gestation (adjusted odds ratio (AOR) 1.7, 95% CI 1.50-1.93), decreasing birthweight ratio (small for gestational age) (AOR 1.3, 95% CI 1.08-1.53), antepartum haemorrhage as primary complication (AOR 3.1, 95% CI 1.25-7.69) and any antenatal steroids (AOR 0.26, 95% CI 0.14-0.51). In comparison with other studies, survival in the extremely preterm group, defined as a gestational age of less than 28 weeks, is improving. CONCLUSIONS: Very preterm infants account for a large proportion of perinatal mortality. Further studies are required to explore the differences between infants on the basis of the primary obstetric complication and to ensure that increased survival is not associated with an increase in disabilities.

Abortion, Induced↗

Neonatal chronic lung disease, oxygen dependency, and a family history of asthma.

We examined the relationship between a family history of asthma (FHA), neonatal chronic lung disease (CLD), and oxygen dependency in an inception cohort study of all 24- to 30-week gestation infants admitted to the sole tertiary perinatal center in Western Australia. One hundred and forty-four infants were admitted during the study period; 116 had data analyzed, 112 of whom survived to discharge. Respiratory morbidity was common and the prevalence increased with decreasing gestation. Hyaline membrane disease (HMD) occurred in 92 (79%) and CLD (oxygen dependency at 28 days) in 62 (53%); 35 (30%) were oxygen dependent at 36 weeks corrected age, and 16 (14%) were oxygen dependent at term. Thirty-two infants had an FHA which was equally distributed between those infants with and without CLD. Infants with an FHA were more likely to be oxygen dependent at term (relative risk 4.4; 95% Cl 1.7,11.1). Thirty-eight percent of mothers smoked; 68% of their infants developed HMD compared to 89% of those whose mothers did not smoke. Logistic regression identified GA<28 weeks (OR 7.3; 95% Cl 1.4,39), severe HMD (OR 4.8; 95% Cl 1.1,22), and FHA (OR 11.0; 95% Cl 2.3,53) as the only factors associated with an increased risk of being oxygen dependent at term. The duration of supplemental oxygen in infants with CLD was significantly related to decreasing gestation, greater degree of barotrauma, presence of HMD, pregnancy-induced hypertension in the mother, duration of patent ductus arteriosus, and an FHA. An FHA may worsen chronic lung disease in the neonate, but is not involved as a causal factor. Clinicians should be aware of its influence on duration of oxygen supplementation when counselling parents of very preterm infants.

Asthma↗

Idazoxan-induced reductions in cortical glucose use are accompanied by an increase in noradrenaline release: complementary [14C]2-deoxyglucose and microdialysis studies.

The autoradiographic [14C]2-deoxyglucose procedure was used to map function-related alterations in local cerebral glucose use following acute administration of the alpha 2-adrenoceptor antagonist, idazoxan (0.3-3 mg kg-1 s.c.). The most prominent feature of the results obtained was the significant reduction in glucose use in certain locus coeruleus projection areas. Thus, in various cortical, hippocampal and thalamic regions, as well as structures involved in auditory and visual function, idazoxan administration was associated with a 13-20% decrease in glucose use. In a complementary microdialysis study, the effect of idazoxan on extracellular noradrenaline levels in the frontal cortex of rats, manipulated in the same fashion as during the [14C]2-deoxyglucose procedure (i.e. following the application of surgery and partial restraint), was examined. Both surgery and restraint were associated with a modest but significant increase in basal noradrenaline release (+31% and +26%, respectively). Subsequent administration of idazoxan (3 mg kg-1 s.c.) evoked a further increase in noradrenaline release, the magnitude of which was the same as that observed following its administration to freely-moving rats (+113%). These combined data suggest that idazoxan-induced reductions in cerebral glucose use, at least in the frontal cortex, may occur as a consequence of the increase in noradrenaline release. In addition, it appears that surgery and partial restraint do not alter alpha 2-adrenoceptor tone in the frontal cortex.

Adrenergic alpha-Antagonists↗

Alpha 2-adrenoceptors and I2 sites in the mammalian central nervous system.

The presence of alpha 2-adrenoceptors and I2 sites in the central nervous system is well established. This review provides a complete summary of this literature, commencing with the first description of alpha 2-adrenoceptors and I2 sites in the brain and covering in detail their subclassification, distribution, and function. Furthermore, it highlights some important differences between central alpha 2-adrenoceptors and I2 sites.

Animals↗

Blowfly strike in England and Wales: the relationship between prevalence and farm and management factors.

In order to develop and evaluate control strategies for blowfly strike, a greater understanding of the epidemiology is essential. A postal survey of sheep farmers yielded information about ten farm and management factors and their relationship to blowfly strike prevalence. The risk of a farm reporting at least one case of blowfly strike increased as flock size and stocking density increased (adjusted odds ratio of 1.13 for an increase in flock size of 100 sheep and 1.38 for an increase in stocking density of ten sheep per hectare). As farm altitude increased, the risk of blowfly strike decreased (adjusted odds ratio 0.67 for an increase in farm altitude of 100 m). The risk of high strike prevalence (more than 2% of sheep struck) decreased as both farm altitude and flock size increased. High strike prevalence was also associated with on-farm sheep carcase disposal (odds ratio 1.35). Farmers in the south-west of England were more likely to report at least one case of blowfly strike and high strike prevalence compared to all other regions.

Agriculture↗

Development of an attractive target for the sheep blowfly Lucilia sericata.

Coloured, odour-baited, sticky targets, designed to catch the sheep blowfly Lucilia sericata Meigen are described and the results of field trials are presented. The number of L. sericata caught by the targets was positively related to target surface area and was dependent on target colour. The performance of the coloured targets is described by a model in which catch is related negatively to reflectivity in the 300-450 nm (ultra-violet/blue) band of the spectrum and positively to the reflectivity in the 450-580 nm (blue-green-yellow) band. Of the Lucilia blowflies caught by the targets, 13-16% were L.sericata and 72-75% of the L.sericata were female. The number of L.sericata caught appeared to be positively related to the availability of sheep over a relatively localized area and showed a marked decline following insecticidal dipping of sheep. The further development of targets and the implications of the results for L.sericata control are discussed.

Animals↗

Effects of feeding frequency and exogenous somatotropin on lipolysis, hormone profiles, and milk production in dairy cows.

Effects of feeding frequency and exogenous bovine somatotropin on lactational performance and hormone profiles were examined with 12 multiparous Holstein cows. At 45 d postpartum, cows were assigned to one of two feeding systems. Concentrates were offered in two equal portions at 0800 and 1600 h or in 12 equal portions at 2-h intervals. Chopped alfalfa hay (2.6 kg/d) and barley silage (ad libitum) were fed at 0900 and 1500 h. At 136 d postpartum, cows within each feeding frequency were assigned in a single crossover design to injection of 30 mg of bST/d or solubilization vehicle. Feeding frequency did not influence any of the parameters measured nor did bST interact with feeding frequency. Somatotropin injection increased daily milk yield of cows by 4.4 kg and concentrations of fat and lactose in milk. Protein concentration and fatty acid composition of milk were not influenced by bST injection. Average plasma somatotropin concentrations were elevated threefold, peak concentrations were increased sevenfold, and concentrations at 48 h postinjection were 1.5 times control values. Plasma insulin concentrations were decreased by bST treatment. Results indicate that responses to short-term bST injection are not influenced by feeding frequency.

Animals↗